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    Clinical Trial Results:
    A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors

    Summary
    EudraCT number
    2012-002206-52
    Trial protocol
    BE   GB   DK  
    Global end of trial date
    28 Feb 2020

    Results information
    Results version number
    v2(current)
    This version publication date
    07 May 2021
    First version publication date
    13 Mar 2021
    Other versions
    v1
    Version creation reason

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CD-ON-MEDI4736-1108
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01693562
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, United States, 20878
    Public contact
    Ashok Gupta, MedImmune, LLC, +1 3013981287, information.center@astrazeneca.com
    Scientific contact
    Ashok Gupta, MedImmune, LLC, +1 3013981287, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Apr 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Feb 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of the study are: 1. To determine maximum tolerated dose or optimal biologic dose of MEDI4736 in dose-escalation phase 2. Safety profile of MEDI4736 in dose-escalation, dose-exploration, dose-expansion phases 3. Antitumor activity of MEDI4736 in dose-expansion phase in participants with programmed death ligand 1 (PD-L1) positive urothelial bladder cancer (UBC) who had received 1 line of prior therapy (2L+), in participants with non-squamous non-small cell lung cancer (NSCLC) who had received 2 or more lines of prior therapy (3L+), and in participants with squamous NSCLC who had received 1 line of prior therapy (2L+) and 2 or more lines of prior therapy (3L+). Antitumor activity was assessed by Blinded Independent Central Review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Aug 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    5 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 55
    Country: Number of subjects enrolled
    Korea, Republic of: 73
    Country: Number of subjects enrolled
    Taiwan: 3
    Country: Number of subjects enrolled
    United States: 681
    Country: Number of subjects enrolled
    Belgium: 29
    Country: Number of subjects enrolled
    France: 66
    Country: Number of subjects enrolled
    Germany: 29
    Country: Number of subjects enrolled
    Italy: 47
    Country: Number of subjects enrolled
    United Kingdom: 41
    Worldwide total number of subjects
    1024
    EEA total number of subjects
    171
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    570
    From 65 to 84 years
    448
    85 years and over
    6

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted in Belgium, Canada, France, Germany, Italy, South Korea, Taiwan, UK, and USA.

    Pre-assignment
    Screening details
    N=1022 participants were enrolled, not N=1024 indicated in participant flow. Discrepancy is due to duplicate reporting of n=2 NSCLC participants. Once in 10mg/kg dose-escalation cohort (total N=6) and again in with N=302 NSCLC participants from 10mg/kg dose expansion cohort (total N=304).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)
    Arm description
    Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 0.1 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Arm description
    Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 0.3 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Escalation Cohort (MEDI4736 1 mg/kg Q2W)
    Arm description
    Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 1 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Escalation Cohort (MEDI4736 3 mg/kg Q2W)
    Arm description
    Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 3 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Escalation Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Arm description
    Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 15 mg/kg was administered as IV infusion Q3W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Arm description
    Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 20 mg/kg was administered as IV infusion Q4W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Arm title
    Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Arm description
    Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.
    Arm type
    Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Durvalumab 10 mg/kg was administered as IV infusion Q2W for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Number of subjects in period 1
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Started
    4
    4
    3
    3
    6
    7
    21
    62
    22
    304
    40
    21
    24
    51
    40
    31
    201
    20
    47
    20
    21
    62
    10
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    0
    0
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    Not completed
    4
    4
    3
    3
    6
    7
    21
    62
    22
    300
    40
    21
    23
    51
    40
    31
    197
    20
    47
    20
    21
    62
    10
         Adverse event, serious fatal
    1
    1
    -
    1
    1
    1
    8
    14
    8
    88
    10
    5
    7
    19
    8
    13
    71
    2
    8
    1
    9
    14
    4
         Consent withdrawn by subject
    -
    1
    -
    -
    -
    2
    2
    16
    2
    54
    2
    2
    3
    5
    16
    7
    40
    4
    8
    3
    1
    8
    1
         Death
    3
    1
    -
    2
    5
    3
    9
    28
    9
    120
    20
    3
    12
    23
    15
    10
    57
    14
    28
    15
    8
    21
    3
         Unspecified
    -
    -
    2
    -
    -
    1
    2
    3
    1
    28
    4
    7
    -
    1
    1
    -
    28
    -
    1
    -
    1
    17
    1
         Lost to follow-up
    -
    1
    1
    -
    -
    -
    -
    1
    2
    10
    4
    4
    1
    3
    -
    1
    1
    -
    2
    1
    2
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)
    Reporting group description
    Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 1 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Reporting group description
    Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Reporting group description
    Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) Total
    Number of subjects
    4 4 3 3 6 7 21 62 22 304 40 21 24 51 40 31 201 20 47 20 21 62 10 1024
    Age categorical
    Units: Participants
        In utero
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    2 0 1 2 6 4 12 41 19 146 26 12 14 33 35 16 77 16 30 15 9 47 7 570
        From 65-84 years
    2 4 2 1 0 3 9 20 3 156 14 9 10 18 5 15 122 4 16 5 12 15 3 448
        85 years and over
    0 0 0 0 0 0 0 1 0 2 0 0 0 0 0 0 2 0 1 0 0 0 0 6
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    58.5 ( 9.0 ) 68.0 ( 2.9 ) 65.3 ( 19.3 ) 57.0 ( 13.7 ) 48.8 ( 9.7 ) 55.9 ( 16.9 ) 64.9 ( 9.6 ) 58.2 ( 12.0 ) 53.5 ( 10.2 ) 63.8 ( 11.0 ) 58.1 ( 14.0 ) 58.9 ( 14.3 ) 61.3 ( 10.2 ) 58.1 ( 11.5 ) 51.2 ( 10.6 ) 62.6 ( 10.2 ) 66.1 ( 9.4 ) 56.0 ( 13.0 ) 59.7 ( 12.5 ) 53.2 ( 15.7 ) 64.8 ( 11.6 ) 54.3 ( 13.4 ) 54.0 ( 19.0 ) -
    Sex: Female, Male
    Units: Participants
        Female
    2 1 2 2 2 2 5 9 15 133 8 9 10 13 40 9 58 7 47 15 8 34 3 434
        Male
    2 3 1 1 4 5 16 53 7 171 32 12 14 38 0 22 143 13 0 5 13 28 7 590
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Asian
    0 0 0 1 0 0 0 5 1 58 9 0 0 1 2 0 40 0 4 1 2 6 5 135
        Black or African American
    0 1 0 0 0 0 1 1 2 10 3 1 0 1 6 1 8 0 1 1 1 2 0 40
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 1 0 0 2 0 0 0 0 0 0 0 0 0 0 0 2 5
        White
    4 3 2 2 6 7 19 49 19 227 19 19 19 45 25 29 128 19 36 18 17 34 3 749
        Other
    0 0 0 0 0 0 1 2 0 4 1 0 0 0 1 1 5 1 0 0 1 4 0 21
        Multiple
    0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 2
        Missing
    0 0 1 0 0 0 0 4 0 5 6 1 5 3 6 0 19 0 6 0 0 16 0 72
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 0 0 0 1 1 2 5 1 12 2 2 1 4 0 1 5 2 2 5 1 4 0 52
        Not Hispanic or Latino
    3 4 2 3 5 6 19 54 21 287 32 19 18 43 33 30 177 18 39 15 20 42 10 900
        Unknown or Not Reported
    0 0 1 0 0 0 0 3 0 5 6 0 5 4 7 0 19 0 6 0 0 16 0 72

    End points

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    End points reporting groups
    Reporting group title
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)
    Reporting group description
    Participants received intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 1 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Reporting group description
    Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Reporting group description
    Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with gastroesophageal cancer (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation or dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion Non-squamous NSCLC 3L+ Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with non-squamous NSCLC who had received 2 or more lines of prior therapy (3L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion Squamous NSCLC 3L+ Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with squamous NSCLC who had received 2 or more lines of prior therapy (3L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion Squamous NSCLC 2L+ Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with squamous NSCLC who had received at least 1 line of prior therapy (2L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion UC PD-L1 high 2L+ Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with UC (post-platinum PD-L1 status high) who had received at least 1 line of prior therapy (2L+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Total Escalation/Exploration Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received IV infusion of MEDI4736 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg Q2W, and 15 mg/kg Q3W in the dose-escalation phase; and 20 mg/kg Q4W in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion UC PD-L1 low/Negative Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with UC (PD-L1 status low/negative) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion UC Total Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with UC (Total PD-L1 status - high, low/negative, and unknown) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Subject analysis set title
    Expansion UC PD-L1 high Cohort
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with UC (PD-L1 status high) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Primary: Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase

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    End point title
    Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase [1] [2]
    End point description
    A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose. Participants in DLT-evaluable population (participants in the dose-escalation phase who received at least 2 doses of study drug and completed safety follow-up through DLT-evaluable period or experienced any DLT during the DLT-evaluation period) were analysed.
    End point type
    Primary
    End point timeframe
    For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Number of subjects analysed
    4
    4
    3
    3
    6
    7
    Units: Participants
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase

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    End point title
    Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [3] [4]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of these outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarised as a total only because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-programmed cell death ligand (PD-L1/PD-1) drug class.
    End point type
    Primary
    End point timeframe
    From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    4
    4
    3
    3
    7
    21
    980
    Units: Participants
        Any TEAEs
    3
    4
    3
    3
    7
    21
    963
        Any TESAEs
    1
    2
    1
    1
    3
    13
    536
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion phase

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    End point title
    Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion phase [5] [6]
    End point description
    Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry. As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarised as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    End point type
    Primary
    End point timeframe
    From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    4
    4
    3
    3
    7
    21
    980
    Units: Participants
        Anaemia
    1
    0
    0
    0
    0
    0
    166
        Thrombocytopenia
    0
    0
    0
    0
    0
    1
    24
        White blood cell count increased
    0
    0
    0
    0
    0
    1
    3
        Leukocytosis
    0
    0
    0
    0
    0
    0
    20
        Lymphocyte count decreased
    0
    0
    0
    0
    0
    0
    12
        Neutropenia
    0
    0
    0
    0
    0
    0
    8
        Leukopenia
    0
    0
    0
    0
    0
    0
    7
        Thrombocytosis
    0
    0
    0
    0
    0
    0
    5
        Iron deficiency anaemia
    0
    0
    0
    0
    0
    0
    3
        Haemoglobin decreased
    0
    0
    0
    0
    0
    0
    2
        Neutrophil count increased
    0
    0
    0
    0
    0
    0
    2
        Red blood cell count decreased
    0
    0
    0
    0
    0
    0
    1
        Anaemia of chronic disease
    0
    0
    0
    0
    0
    0
    1
        Eosinophilia
    0
    0
    0
    0
    0
    0
    1
        Haemolysis
    0
    0
    0
    0
    0
    0
    1
        Leukostasis syndrome
    0
    0
    0
    0
    0
    0
    1
        Immune thrombocytopenic purpura
    0
    0
    0
    0
    0
    0
    1
        International normalised ratio increased
    0
    0
    0
    0
    0
    0
    16
        Activated partial thromboplastin time prolonged
    0
    0
    0
    0
    0
    0
    15
        Blood fibrinogen increased
    0
    0
    0
    0
    0
    0
    8
        Platelet count decreased
    0
    0
    0
    0
    0
    0
    5
        Disseminated intravascular coagulation
    0
    0
    0
    0
    0
    0
    2
        Prothrombin time prolonged
    0
    0
    0
    0
    0
    0
    2
        Activated partial thromboplastin time shortened
    0
    0
    0
    0
    0
    0
    1
        Coagulation factor increased
    0
    0
    0
    0
    0
    0
    1
        Coagulopathy
    0
    0
    0
    0
    0
    0
    1
        Alanine aminotransferase increased
    0
    0
    1
    0
    1
    2
    77
        Aspartate aminotransferase increased
    0
    0
    1
    0
    1
    2
    99
        Blood alkaline phosphatase increased
    0
    0
    1
    0
    0
    1
    70
        Blood bilirubin increased
    0
    0
    0
    0
    0
    1
    42
        Gamma-glutamyltransferase increased
    0
    0
    0
    0
    0
    2
    71
        Hyperbilirubinaemia
    0
    0
    0
    0
    0
    0
    14
        Transaminases increased
    0
    0
    0
    0
    0
    0
    8
        Blood lactate dehydrogenase increased
    0
    0
    0
    0
    0
    0
    7
        Hepatic function abnormal
    0
    0
    0
    0
    0
    0
    6
        Alanine aminotransferase decreased
    0
    0
    0
    0
    0
    0
    1
        Aspartate aminotransferase decreased
    0
    0
    0
    0
    0
    0
    1
        Blood albumin decreased
    0
    0
    0
    0
    0
    0
    1
        Hepatic enzyme increased
    0
    0
    0
    0
    0
    0
    1
        Liver function test increased
    0
    0
    0
    0
    0
    0
    1
        White blood cell count decreased
    0
    0
    0
    0
    0
    0
    8
        Neutrophil count decreased
    0
    0
    0
    0
    0
    0
    5
        Lymphopenia
    0
    0
    0
    0
    0
    0
    5
        Blood creatinine increased
    0
    1
    1
    0
    0
    0
    46
        Hyperuricaemia
    0
    0
    0
    0
    0
    0
    22
        Blood urea increased
    0
    0
    0
    0
    0
    0
    10
        Glomerular filtration rate decreased
    0
    0
    0
    0
    0
    0
    2
        Hypothyroidism
    0
    1
    1
    0
    1
    3
    89
        Hyperthyroidism
    0
    0
    0
    0
    0
    1
    30
        Blood thyroid stimulating hormone increased
    0
    0
    0
    0
    0
    0
    16
        Blood thyroid stimulating hormone decreased
    0
    0
    0
    0
    0
    0
    5
        Thyroxine decreased
    0
    0
    0
    0
    0
    0
    2
        Thyroxine free decreased
    0
    0
    0
    0
    0
    0
    2
        Thyroxine free increased
    0
    0
    0
    0
    0
    0
    2
        Tri-iodothyronine free decreased
    0
    0
    0
    0
    0
    0
    2
        Thyroxine increased
    0
    0
    0
    0
    0
    0
    1
        Tri-iodothyronine decreased
    0
    0
    0
    0
    0
    0
    1
        Tri-iodothyronine increased
    0
    0
    0
    0
    0
    0
    1
        Hyponatraemia
    0
    0
    1
    0
    1
    1
    91
        Hypomagnesaemia
    0
    0
    0
    0
    0
    1
    55
        Hypercalcaemia
    0
    0
    0
    0
    0
    0
    47
        Hyperglycaemia
    0
    0
    1
    0
    0
    0
    32
        Hypokalaemia
    0
    0
    0
    0
    0
    0
    60
        Hypocalcaemia
    0
    0
    0
    0
    0
    0
    17
        Hypophosphataemia
    0
    0
    0
    0
    0
    0
    16
        Hypertriglyceridaemia
    0
    0
    0
    0
    0
    0
    13
        Hypoglycaemia
    0
    0
    0
    0
    0
    0
    10
        Blood cholesterol increased
    0
    0
    0
    0
    0
    0
    6
        Blood magnesium decreased
    0
    0
    0
    0
    0
    0
    5
        Blood triglycerides increased
    0
    0
    0
    0
    0
    0
    5
        Blood glucose increased
    0
    0
    0
    0
    0
    0
    4
        Hypercholesterolaemia
    0
    0
    0
    0
    0
    0
    4
        Blood potassium increased
    0
    0
    0
    0
    0
    0
    3
        Blood chloride increased
    0
    0
    0
    0
    0
    0
    2
        Blood electrolytes decreased
    0
    0
    0
    0
    0
    0
    2
        Blood potassium decreased
    0
    0
    0
    0
    0
    0
    2
        Hyperphosphataemia
    0
    0
    0
    0
    0
    0
    2
        Protein total decreased
    0
    0
    0
    0
    0
    0
    2
        Protein urine present
    0
    0
    0
    0
    0
    0
    2
        Blood bicarbonate decreased
    0
    0
    0
    0
    0
    0
    1
        Blood chloride decreased
    0
    0
    0
    0
    0
    0
    1
        Blood sodium decreased
    0
    0
    0
    0
    0
    0
    1
        Hypermagnesaemia
    0
    0
    0
    0
    0
    0
    1
        Hypernatraemia
    0
    0
    0
    0
    0
    0
    1
        Hypochloraemia
    0
    0
    0
    0
    0
    0
    1
        Hypoproteinaemia
    0
    0
    0
    0
    0
    0
    1
        Hyperkalaemia
    0
    0
    0
    0
    0
    0
    30
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase

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    End point title
    Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [7] [8]
    End point description
    Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate). As-treated population included all participants who received any dose of study drug. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarised as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    End point type
    Primary
    End point timeframe
    From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    4
    4
    3
    3
    7
    21
    980
    Units: Participants
        Pyrexia
    0
    3
    0
    1
    3
    2
    145
        Weight decreased
    0
    0
    0
    0
    0
    2
    79
        Hypertension
    0
    1
    0
    1
    0
    0
    31
        Hypotension
    0
    0
    0
    0
    0
    1
    36
        Weight increased
    0
    0
    0
    0
    0
    0
    22
        Tachycardia
    0
    0
    0
    0
    0
    0
    19
        Sinus tachycardia
    0
    0
    0
    0
    0
    0
    14
        Arrhythmia
    0
    0
    0
    0
    0
    0
    3
        Sinus bradycardia
    0
    0
    0
    0
    0
    0
    3
        Heart rate increased
    0
    0
    0
    0
    0
    0
    1
        Heart rate irregular
    0
    0
    0
    0
    0
    0
    1
        Peak expiratory flow rate decreased
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase

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    End point title
    Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [9] [10]
    End point description
    Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram are reported. The data for >0 participants with notable QT/QTc interval in local electrocardiogram from baseline are reported. As-treated population included all participants who received any dose of study drug were analysed. Participants with ECG readings available were evaluable for this analysis. Participants enrolled in the 10 mg/kg Q2W Expansion and Escalation Cohort have been summarised as a total only. This is because the safety profile of durvalumab monotherapy 10 mg/kg Q2W was manageable and generally consistent with the known safety profile of the anti-PD-L1/PD-1 drug class.
    End point type
    Primary
    End point timeframe
    From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Escalation/Expansion Cohort (Total MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    4
    4
    3
    3
    7
    21
    980
    Units: Participants
        QTcF: > 30 (msec) n=0,1,1,1,0,0,63
    0
    1
    0
    0
    0
    0
    4
        QTcF: > 60 (msec) n=0,1,1,1,0,0,63
    0
    1
    0
    0
    0
    0
    0
        QTcB: > 30 (msec) n=2,2,2,1,2,9,288
    0
    0
    0
    0
    0
    4
    17
        QTcB: > 60 (msec) n=2,2,2,1,2,9,288
    0
    0
    0
    0
    0
    0
    4
        QTcB: > 90 (msec) n=4,4,3,3,7,21,288
    0
    0
    0
    0
    0
    0
    3
    No statistical analyses for this end point

    Primary: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC who had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase

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    End point title
    Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC who had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase [11]
    End point description
    The ORR assessed by BICR is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. The CR is disappearance of all target & non-target lesions & no new lesions. A confirmed CR is 2 CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is >= 30% decrease in sum of diameters of target lesions (compared to baseline) & no new nontarget lesion. A confirmed PR is 2 PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 wks with no evidence of progression in-between. Participants with non-squamous NSCLC in Full analysis set (FAS) population who had received 2 or more prior line of therapy were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    End point type
    Primary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Expansion Non-squamous NSCLC 3L+ Cohort
    Number of subjects analysed
    68
    Units: Percentage of participants
        number (confidence interval 95%)
    10.3 (4.2 to 20.1)
    No statistical analyses for this end point

    Primary: ORR Assessed by BICR in Participants With Squamous NSCLC who had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase

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    End point title
    ORR Assessed by BICR in Participants With Squamous NSCLC who had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase [12]
    End point description
    The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. Participants with squamous NSCLC in FAS population who had received 1 and 2 or more prior line of therapy were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    End point type
    Primary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Expansion Squamous NSCLC 3L+ Cohort Expansion Squamous NSCLC 2L+ Cohort
    Number of subjects analysed
    62
    117
    Units: Percentage of participants
        number (confidence interval 95%)
    12.9 (5.7 to 23.9)
    12.8 (7.4 to 20.3)
    No statistical analyses for this end point

    Primary: ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) who had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase

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    End point title
    ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) who had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase [13]
    End point description
    The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is disappearance of all target and non-target lesions and no new lesions. A confirmed CR is 2 CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is 2 PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 wks with no evidence of progression in-between. Participants with UC in FAS population with 2L+ post-platinum PD-L1 status high (>= 25% tumor cell membrane or >= 25% immune cell staining) were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017.
    End point type
    Primary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Expansion UC PD-L1 high 2L+ Cohort
    Number of subjects analysed
    98
    Units: Percentage of participants
        number (confidence interval 95%)
    27.6 (19.0 to 37.5)
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase

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    End point title
    Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase [14]
    End point description
    Area under the concentration-time curve from time zero to the last measurable concentration (AUClast) of MEDI4736 is reported. Pharmacokinetics (PK) evaluable population included all participants who received any dose of study drug and had at least one postdose PK concentration. Non-compartmental PK analysis was conducted using the data from dose escalation and exploration phases only.
    End point type
    Secondary
    End point timeframe
    After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Number of subjects analysed
    4
    4
    3
    3
    5
    7
    18
    Units: Day*µg/mL
        geometric mean (geometric coefficient of variation)
    5.144 ( 45.1 )
    25.063 ( 65.5 )
    130.546 ( 20.1 )
    399.863 ( 21.7 )
    1780.152 ( 39.1 )
    2943.770 ( 36.3 )
    4501.888 ( 23.1 )
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase

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    End point title
    Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase [15]
    End point description
    Maximum Serum Concentration (Cmax) of MEDI4736 is reported. PK evaluable population included all participants who received any dose of study drug and had at least one postdose PK concentration. Non-compartmental PK analysis was conducted using the data from dose escalation and exploration phases only.
    End point type
    Secondary
    End point timeframe
    After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Number of subjects analysed
    4
    4
    3
    3
    5
    7
    18
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    2.780 ( 22.1 )
    7.969 ( 23.0 )
    22.773 ( 11.3 )
    70.807 ( 17.0 )
    293.540 ( 23.4 )
    427.085 ( 25.5 )
    416.051 ( 23.9 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase.

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    End point title
    Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase. [16]
    End point description
    Number of participants with positive ADA titer to MEDI4736 are reported. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive. ADA evaluable population included all participants who received any dose of study drug, had non-missing baseline (before Day 1) ADA, and at least one non-missing post-baseline ADA results.
    End point type
    Secondary
    End point timeframe
    Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) Total Escalation/Exploration Cohort
    Number of subjects analysed
    56
    17
    257
    37
    17
    21
    38
    33
    26
    148
    17
    41
    19
    15
    58
    6
    45
    Units: Participants
        Positive post-baseline
    1
    0
    6
    0
    0
    1
    0
    1
    0
    7
    0
    2
    1
    0
    2
    0
    4
        Treatment-boosted
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
        Persistent positive
    1
    0
    4
    1
    0
    1
    0
    1
    1
    5
    0
    0
    1
    0
    1
    0
    2
        Transient positive
    0
    0
    2
    0
    0
    0
    0
    0
    0
    3
    0
    2
    0
    0
    1
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase

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    End point title
    Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase [17]
    End point description
    The BOR assessed by BICR in NSCLC and SCCHN cohort is reported. The BOR includes CR, PR, stable disease (SD), progressive disease (PD), & non-evaluable (NE). The CR is disappearance of all target & nontarget lesions & no new lesions. The PR is >= 30% decrease in the sum of diameters of target lesions (compared to baseline [BL]) & no new nontarget lesion. The PD is atleast 20% decrease in sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is when no or only a subset of lesion measurements are made at an assessment. Participants in FAS population with NSCLC and SCCHN were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at BL (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    55
    275
    Units: Participants
        CR
    0
    3
        PR
    4
    39
        SD
    10
    80
        PD
    31
    110
        NE
    10
    43
    No statistical analyses for this end point

    Secondary: Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase

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    End point title
    Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase [18]
    End point description
    The BOR assessed by investigator based on RECIST v1.1 is reported. The BOR includes CR, PR, SD, PD, and NE. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. As-treated population included all participants who received any dose of study drug. One participant from non-SCCHN HPV positive cohort had non-evaluable disease at baseline.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) Total Escalation/Exploration Cohort
    Number of subjects analysed
    62
    22
    304
    40
    21
    24
    51
    40
    31
    201
    20
    47
    20
    21
    62
    10
    48
    Units: Participants
        CR
    1
    1
    5
    0
    1
    0
    1
    0
    0
    18
    0
    1
    0
    0
    3
    0
    1
        PR
    6
    2
    49
    4
    2
    1
    1
    1
    1
    24
    0
    2
    2
    2
    12
    3
    4
        SD
    14
    7
    102
    22
    9
    8
    17
    8
    6
    45
    5
    18
    8
    4
    27
    2
    18
        PD
    33
    9
    103
    12
    5
    12
    21
    25
    17
    81
    14
    22
    8
    9
    15
    3
    18
        NE
    8
    2
    43
    2
    4
    3
    11
    6
    7
    33
    1
    4
    2
    6
    5
    2
    7
        Not applicable
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase

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    End point title
    Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase [19]
    End point description
    DoR assessed by BICR is reported, which is duration from 1st documentation of objective response (OR) (confirmed 2 CRs [disappearance of all target and non-target lesions and no new lesions] or confirmed 2 PRs [>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion]) to 1st documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. DoR was estimated using Kaplan-Meier method. Arbitrary number 99999 signified upper limit of CI, which was not derived due to insufficient events being observed at time of analysis. Participants in FAS population (participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017) with NSCLC and SCCHN were analysed. DoR was analysed for those participants who achieved OR.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    4
    42
    Units: Months
        median (confidence interval 95%)
    12.37 (3.5 to 99999)
    17.74 (5.6 to 38.0)
    No statistical analyses for this end point

    Secondary: DoR assessed by Investigator in the Dose-expansion Phase

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    End point title
    DoR assessed by Investigator in the Dose-expansion Phase [20]
    End point description
    The DoR assessed by investigator is reported which is defined as the duration from the first documentation of OR (confirmed 2 CRs or confirmed 2 PRs) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The arbitrary numbers 0.9999, 99999, & 99.999 signified the lower limit and upper limit of confidence interval, and median, respectively, which were not derived due to insufficient events being observed at the time of the analysis. As-treated population included all participants who received any dose of study drug. The DoR was analysed for those participants who achieved OR.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    7
    3
    54
    4
    3
    1
    2
    1
    1
    42
    0 [21]
    3
    2
    2
    15
    3
    Units: Months
        median (confidence interval 95%)
    19.71 (1.9 to 44.0)
    14.75 (12.8 to 99999)
    9.95 (8.3 to 16.4)
    16.20 (7.2 to 99999)
    99.999 (7.9 to 99999)
    9.23 (0.9999 to 99999)
    99.999 (0.9999 to 99999)
    99.999 (0.9999 to 99999)
    5.36 (0.9999 to 99999)
    99.999 (14.6 to 99999)
    ( to )
    24.87 (4.8 to 24.9)
    7.92 (6.1 to 9.7)
    23.51 (14.6 to 32.4)
    26.91 (12.7 to 99999)
    8.64 (4.4 to 16.3)
    Notes
    [21] - No participants achieved OR.
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase

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    End point title
    Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN cohort in the Dose-expansion Phase [22]
    End point description
    Percentage of participants with DCR assessed by BICR is reported. The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is 2 PRs (>= 30% decrease in sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Participants in FAS population with NSCLC and SCCHN were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    55
    275
    Units: Percentage of participants
        number (confidence interval 95%)
    25.5 (14.7 to 39.0)
    44.4 (38.4 to 50.5)
    No statistical analyses for this end point

    Secondary: DCR Assessed by Investigator in the Dose-expansion Phase

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    End point title
    DCR Assessed by Investigator in the Dose-expansion Phase [23]
    End point description
    The DCR assessed by investigator is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is 2 CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is 2 PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The arbitrary numbers -0.9999 and 99999 signified the lower limit and upper limit of CI, which were not derived due to insufficient events being observed at the time of the analysis. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    62
    22
    302
    40
    21
    24
    51
    40
    31
    201
    20
    47
    20
    21
    62
    10
    Units: Percentage of participants
        number (confidence interval 95%)
    33.9 (22.3 to 47.0)
    45.5 (25.7 to 70.2)
    51.7 (45.9 to 57.4)
    65.0 (48.3 to 79.4)
    57.1 (34.0 to 78.2)
    37.5 (18.8 to 59.4)
    37.3 (24.1 to 51.9)
    22.5 (10.8 to 38.5)
    22.6 (9.6 to 41.1)
    43.3 (36.3 to 50.4)
    0 (-0.9999 to 99999)
    44.7 (30.2 to 59.9)
    50.0 (27.2 to 72.8)
    28.6 (11.3 to 52.2)
    67.7 (54.7 to 79.1)
    50.0 (18.7 to 81.3)
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS) Assessed by BICR in NSCLC cohort in the Dose-expansion Phase

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    End point title
    Progression-free Survival (PFS) Assessed by BICR in NSCLC cohort in the Dose-expansion Phase [24]
    End point description
    The PFS assessed by BICR in NSCLC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. Participants in As-treated population with NSCLC were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    304
    Units: Percentage of participants
        median (confidence interval 95%)
    2.1 (1.5 to 2.6)
    No statistical analyses for this end point

    Secondary: PFS Assessed by BICR in SCCHN cohort in the Dose-expansion Phase

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    End point title
    PFS Assessed by BICR in SCCHN cohort in the Dose-expansion Phase [25]
    End point description
    The PFS assessed by BICR in SCCHN cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. Participants in FAS population with SCCHN were analyzed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    62
    Units: Percentage of participants
        median (confidence interval 95%)
    1.4 (1.3 to 1.5)
    No statistical analyses for this end point

    Secondary: PFS Assessed by Investigator in the Dose-expansion Phase

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    End point title
    PFS Assessed by Investigator in the Dose-expansion Phase [26]
    End point description
    The PFS assessed by the investigator is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    62
    22
    302
    40
    21
    24
    51
    40
    31
    201
    20
    47
    20
    21
    62
    10
    Units: Months
        median (confidence interval 95%)
    1.4 (1.4 to 1.6)
    1.5 (1.2 to 5.6)
    2.6 (1.9 to 3.2)
    2.7 (1.4 to 5.3)
    2.8 (1.2 to 9.1)
    1.4 (1.3 to 4.6)
    1.4 (1.2 to 2.4)
    1.3 (1.2 to 1.6)
    1.5 (1.3 to 1.7)
    1.8 (1.4 to 2.6)
    1.4 (1.2 to 2.3)
    1.8 (1.4 to 2.7)
    2.6 (1.4 to 3.0)
    1.5 (0.9 to 1.8)
    5.4 (2.9 to 11.1)
    2.2 (0.7 to 5.7)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) in the Dose-Expansion Phase

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    End point title
    Overall Survival (OS) in the Dose-Expansion Phase [27]
    End point description
    The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary numbers 99999 and 99.999 signified the data for upper limit of confidence interval and median, respectively, which were not derived due to insufficient events being observed at the time of the analysis. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN HPV+ Cohort (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Number of subjects analysed
    62
    22
    304
    40
    21
    24
    51
    40
    31
    201
    20
    47
    20
    21
    62
    10
    Units: Months
        median (confidence interval 95%)
    8.4 (5.7 to 12.3)
    11.6 (3.0 to 22.8)
    12.4 (9.3 to 15.2)
    13.2 (6.3 to 23.0)
    99.999 (15.1 to 99999)
    8.4 (4.5 to 14.3)
    4.9 (2.6 to 9.1)
    5.5 (3.5 to 16.8)
    5.7 (4.8 to 8.0)
    10.5 (6.9 to 15.7)
    10.0 (6.2 to 13.0)
    11.1 (8.2 to 16.6)
    15.8 (8.1 to 23.3)
    4.8 (1.3 to 10.4)
    24.1 (12.4 to 37.1)
    16.1 (0.9 to 99999)
    No statistical analyses for this end point

    Secondary: ORR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    ORR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The ORR assessed by BICR in UC cohort is reported. The ORR is BOR of confirmed CR (2 CRs separated by at least 28 days with no evidence of progression in-between) or confirmed PR (2 PRs or an un-confirmed PR & an un-confirmed CR separated by at least 4 wks with no evidence of progression in-between) based on RECIST v1.1. The CR is disappearance of all target and non-target lesions and no new lesions. The PR is >= 30% decrease in sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the FAS population were analysed. FAS population included all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 weeks by 16Oct2017.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    85
    199
    101
    Units: Percentage of participants
        number (confidence interval 95%)
    5.9 (1.9 to 13.2)
    17.6 (12.6 to 23.6)
    27.7 (19.3 to 37.5)
    No statistical analyses for this end point

    Secondary: ORR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    ORR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The ORR assessed by the investigator in UC cohort is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    86
    201
    102
    Units: Percentage of participants
        number (confidence interval 95%)
    7.0 (2.6 to 14.6)
    20.9 (15.5 to 27.2)
    33.3 (24.3 to 43.4)
    No statistical analyses for this end point

    Secondary: DoR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    DoR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The DoR assessed by BICR in UC cohort is reported. The DoR is the duration from the first documentation of OR (confirmed 2 CRs or confirmed 2 PRs) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The arbitrary numbers 99999 & 99.999 signified upper limit of confidence interval and median, respectively, which were not derived due to insufficient events being observed at the time of the analysis. The DoR was estimated using Kaplan-Meier method. The UC cohort participants with PD-L1 status as low/negative, total, and high included in the FAS population (participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017) were analysed. The DoR was analysed for those participants who achieved OR.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    5
    35
    28
    Units: Months
        median (confidence interval 95%)
    12.25 (8.6 to 99999)
    99.999 (16.0 to 99999)
    99.999 (16.0 to 99999)
    No statistical analyses for this end point

    Secondary: DoR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    DoR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The DoR assessed by investigator in UC cohort is reported. The DoR is the duration from the first documentation of OR (confirmed 2 CRs or confirmed 2 PRs) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The arbitrary number 99999 signified upper limit of CI, which was not derived due to insufficient events being observed at the time of the analysis. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population (all participants who received any dose of study drug) were analysed. The DoR was analysed for those participants who achieved OR.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    6
    42
    34
    Units: Months
        median (confidence interval 95%)
    14.82 (6.9 to 99999)
    19.71 (14.6 to 99999)
    99.999 (12.3 to 99999)
    No statistical analyses for this end point

    Secondary: DCR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    DCR Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The DCR assessed by BICR in UC cohort is reported, which is defined as BOR of confirmed CR (2 CRs [disappearance of all target and nontarget lesions and no new lesions]), confirmed PR (2 PRs [>= 30% decrease in sum of diameters of target lesions compared to baseline and no new nontarget lesion] or an unconfirmed PR and an unconfirmed CR), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) based on RECIST v1.1. 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The UC cohort participants with PD-L1 status as low/negative, total, and high included in the FAS population (all participants who received any dose of study drug, had measurable disease at baseline (Day 1) per BICR and were followed for at least 24 wks by 16Oct2017) were analysed.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    85
    199
    101
    Units: Percentage of participants
        number (confidence interval 95%)
    21.2 (13.1 to 31.4)
    35.2 (28.6 to 42.2)
    43.6 (33.7 to 53.8)
    No statistical analyses for this end point

    Secondary: DCR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    DCR Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    Percentage of participants with DCR assessed by investigator in UC cohort is reported. The DCR is BOR of confirmed CR, (2 CRs [disappearance of all target and nontarget lesions and no new lesions]), confirmed PR (2 PRs [>= 30% decrease in sum of diameters of target lesions compared to baseline and no new nontarget lesion] or an unconfirmed PR and an unconfirmed CR), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression) based on RECIST v1.1. 2 CRs and/or 2 PRs should be separated by at least 28 days with no evidence of progression in-between. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown) & high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    86
    201
    102
    Units: Percentage of participants
        number (confidence interval 95%)
    30.2 (20.8 to 41.1)
    43.3 (36.3 to 50.4)
    53.9 (43.8 to 63.8)
    No statistical analyses for this end point

    Secondary: PFS Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    PFS Assessed by BICR in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The PFS assessed by BICR in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    86
    201
    102
    Units: Months
        median (confidence interval 95%)
    1.4 (1.3 to 1.5)
    1.5 (1.4 to 1.8)
    1.9 (1.4 to 2.7)
    No statistical analyses for this end point

    Secondary: PFS Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    PFS Assessed by Investigator in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The PFS assessed by the investigator in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    86
    201
    102
    Units: Months
        median (confidence interval 95%)
    1.4 (1.4 to 1.7)
    1.8 (1.4 to 2.6)
    2.8 (1.8 to 3.7)
    No statistical analyses for this end point

    Secondary: OS in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase

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    End point title
    OS in UC Cohort (PD-L1 low/Negative, Total, and PD-L1 high) in the Dose-expansion Phase
    End point description
    The OS in UC cohort is reported. The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary number 99999 signified upper limit of confidence interval which was not derived due to insufficient events being observed at the time of the analysis. The UC cohort participants with PD-L1 status as low/negative (<25% tumor cell membrane and <25% immune cell staining), total (PD-L1 high, PD-L1 low/negative, and PD-L1 unknown), and high (>= 25% tumor cell membrane or >=25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC Total Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    86
    201
    102
    Units: Months
        median (confidence interval 95%)
    4.8 (3.3 to 8.1)
    10.5 (6.9 to 15.7)
    19.8 (9.3 to 99999)
    No statistical analyses for this end point

    Secondary: Adjusted Comparison of PFS by PD-L1 status in UC Cohort in the Dose-expansion Phase

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    End point title
    Adjusted Comparison of PFS by PD-L1 status in UC Cohort in the Dose-expansion Phase
    End point description
    The PFS by PD-L1 status in UC cohort is reported. The PFS estimates are adjusted for baseline eastern cooperative oncology group (ECOG), smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The PFS is the time from the start of study treatment until first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. The UC cohort participants with PD-L1 status as high (>= 25% tumor cell membrane or >=25% immune cell staining) and low/negative (<25% tumor cell membrane and <25% immune cell staining) included in the As-treated population were analysed.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    39
    61
    Units: Months
        median (confidence interval 95%)
    1.5 (1.4 to 2.4)
    2.6 (1.4 to 3.9)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Expansion UC PD-L1 high Cohort v Expansion UC PD-L1 low/Negative Cohort
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    [28]
    P-value
    = 0.016
    Method
    Regression, Cox
    Confidence interval
    Notes
    [28] - Other

    Secondary: Adjusted Comparison of OS by PD-L1 status in UC Cohort in the Dose-expansion Phase

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    End point title
    Adjusted Comparison of OS by PD-L1 status in UC Cohort in the Dose-expansion Phase
    End point description
    The OS by PD-L1 status in UC cohort is reported. The OS estimates are adjusted for baseline ECOG, smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary number 99999 signified upper limit of confidence interval which was not derived due to insufficient events being observed at the time of the analysis. The UC cohort participants with PD-L1 status as high (>= 25% tumor cell membrane or >=25% immune cell staining) and low/negative (<25% tumor cell membrane and <25% immune cell staining) included in the As-treated population were analysed. As-treated population included all participants who received any dose of study drug.
    End point type
    Secondary
    End point timeframe
    From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
    End point values
    Expansion UC PD-L1 low/Negative Cohort Expansion UC PD-L1 high Cohort
    Number of subjects analysed
    39
    61
    Units: Months
        median (confidence interval 95%)
    3.4 (2.4 to 14.3)
    18.4 (7.8 to 99999)
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Expansion UC PD-L1 high Cohort v Expansion UC PD-L1 low/Negative Cohort
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    [29]
    P-value
    = 0.0046
    Method
    Regression, Cox
    Confidence interval
    Notes
    [29] - Other

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)
    Reporting group description
    Participants received intravenous (IV) infusion of MEDI4736 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 3 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 1 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 15 mg/kg Q3W)
    Reporting group description
    Participants received IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Escalation Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Exploration Cohort (MEDI4736 20 mg/kg Q4W)
    Reporting group description
    Participants received IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with squamous cell carcinoma of the head and neck (SCCHN) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion Non-SCCHN Cohort HPV+ (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with non-small-cell lung cancer (NSCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with hepatocellular carcinoma (HCC Total) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with uveal melanoma (UM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with advance cutaneous melanoma (ACM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with gastroesophageal (GEC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with triple-negative breast cancer (TNBC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with urothelial carcinoma (UC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with pancreatic adenocarcinoma (PAC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with glioblastoma multiforme (GBM) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with soft- tissue sarcoma (STS) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with ovarian cancer (OC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with microsatellite instability (MSI)-high cancer received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with small-cell lung cancer (SCLC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Reporting group title
    Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Reporting group description
    Participants with nasopharyngeal carcinoma (NPC) received IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurred first.

    Serious adverse events
    Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) Escalation Cohort (MEDI4736 3 mg/kg Q2W) Escalation Cohort (MEDI4736 1 mg/kg Q2W) Escalation Cohort (MEDI4736 15 mg/kg Q3W) Escalation Cohort (MEDI4736 10 mg/kg Q2W) Exploration Cohort (MEDI4736 20 mg/kg Q4W) Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) Expansion Non-SCCHN Cohort HPV+ (MEDI4736 10 mg/kg Q2W) Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    3 / 6 (50.00%)
    13 / 21 (61.90%)
    30 / 62 (48.39%)
    16 / 22 (72.73%)
    163 / 304 (53.62%)
    24 / 40 (60.00%)
    12 / 24 (50.00%)
    7 / 21 (33.33%)
    26 / 51 (50.98%)
    20 / 40 (50.00%)
    117 / 201 (58.21%)
    25 / 31 (80.65%)
    9 / 20 (45.00%)
    7 / 20 (35.00%)
    26 / 47 (55.32%)
    31 / 62 (50.00%)
    14 / 21 (66.67%)
    7 / 10 (70.00%)
         number of deaths (all causes)
    4
    2
    3
    0
    4
    6
    17
    42
    17
    208
    30
    19
    8
    42
    23
    128
    23
    16
    16
    36
    35
    17
    7
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA OF THE CERVIX
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    1 / 22 (4.55%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ADENOCARCINOMA PANCREAS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 21 (9.52%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    3 / 31 (9.68%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAL CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    3 / 22 (13.64%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BLADDER CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    45 / 201 (22.39%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 50
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 42
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BLADDER CANCER STAGE IV
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    1 / 201 (0.50%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BLADDER TRANSITIONAL CELL CARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    4 / 201 (1.99%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BREAST CANCER METASTATIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    1 / 40 (2.50%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CANCER PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    3 / 201 (1.49%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CERVIX CARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    2 / 22 (9.09%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOROID MELANOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    1 / 24 (4.17%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLON CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    2 / 62 (3.23%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    COLORECTAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    1 / 62 (1.61%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLORECTAL CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    5 / 62 (8.06%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    ENDOMETRIAL CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    1 / 62 (1.61%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    GASTRIC CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    4 / 51 (7.84%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 21 (4.76%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    1 / 51 (1.96%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GLIOBLASTOMA MULTIFORME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    2 / 20 (10.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEPATOCELLULAR CARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    7 / 40 (17.50%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 8
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTRAOCULAR MELANOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    2 / 24 (8.33%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    3 / 304 (0.99%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG CANCER METASTATIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    3 / 304 (0.99%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG NEOPLASM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    1 / 304 (0.33%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG NEOPLASM MALIGNANT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    13 / 304 (4.28%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    1 / 21 (4.76%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 14
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 12
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    MALIGNANT MELANOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    2 / 21 (9.52%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT NEOPLASM OF RENAL PELVIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    1 / 201 (0.50%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT PLEURAL EFFUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    1 / 51 (1.96%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    METASTASES TO BLADDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    1 / 201 (0.50%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    METASTATIC CARCINOMA OF THE BLADDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    1 / 201 (0.50%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    METASTATIC GASTRIC CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    1 / 51 (1.96%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    METASTATIC MALIGNANT MELANOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    1 / 24 (4.17%)
    2 / 21 (9.52%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NASOPHARYNGEAL CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    4 / 10 (40.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    NEOPLASM SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    1 / 304 (0.33%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NON-SMALL CELL LUNG CANCER
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 21 (4.76%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    47 / 304 (15.46%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 55
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 43
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NON-SMALL CELL LUNG CANCER METASTATIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    1 / 304 (0.33%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL ADENOCARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    1 / 51 (1.96%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL CANCER METASTATIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    2 / 51 (3.92%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL CARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    3 / 51 (5.88%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ONCOLOGIC COMPLICATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    1 / 62 (1.61%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    0 / 47 (0.00%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OVARIAN CANCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 21 (0.00%)
    0 / 62 (0.00%)
    0 / 22 (0.00%)
    0 / 304 (0.00%)
    0 / 40 (0.00%)
    0 / 24 (0.00%)
    0 / 21 (0.00%)
    0 / 51 (0.00%)
    0 / 40 (0.00%)
    0 / 201 (0.00%)
    0 / 31 (0.00%)
    0 / 20 (0.00%)
    0 / 20 (0.00%)
    7 / 47 (14.89%)
    0 / 62 (0.00%)
    0 / 21 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 8
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0