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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	v1
This version publication date	13 Mar 2021
First version publication date	13 Mar 2021
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CD-ON-MEDI4736-1108

ISRCTN number

US NCT number

NCT01693562

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

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?

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?

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

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

570

From 65 to 84 years

448

85 years and over

Subject disposition

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Recruitment details

The study was conducted in Belgium, Canada, France, Germany, Italy, South Korea, Taiwan, UK, and USA.

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 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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.

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.

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.

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.

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.

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.

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

Expansion Non-SCCHN Cohort HPV+ (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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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 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	-	-	3	-	-	1	2	3	1	28	4	7	-	1	1	-	28	-	1	-	1	17	1
Lost to follow-up	-	1	-	-	-	-	-	1	2	10	4	4	1	3	-	1	1	-	2	1	2	2	1

Baseline characteristics

Top of page

Reporting group title

Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 1 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 3 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 15 mg/kg Q3W)

Reporting group description

Reporting group title

Exploration Cohort (MEDI4736 20 mg/kg Q4W)

Reporting group description

Reporting group title

Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion Non-SCCHN Cohort HPV+ (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

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 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 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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Reporting group title

Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 1 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 3 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 15 mg/kg Q3W)

Reporting group description

Reporting group title

Exploration Cohort (MEDI4736 20 mg/kg Q4W)

Reporting group description

Reporting group title

Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion Non-SCCHN Cohort HPV+ (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

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: 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.
[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: 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.

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: 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.
[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: 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.

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: 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.
[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: 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.

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: 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.
[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: 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.

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

Top of page

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 and had change from baseline in notable QT/QTc interval in local electrocardiogram were analysed for this outcome measure. 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: 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.
[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: 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.

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: 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.

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: 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.

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: 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.

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: 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.

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

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: 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.

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: 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.

End point values	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 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: 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.

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.

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: 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.

End point values	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 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

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: 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.

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: 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.

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 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

0 ^[21]

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)

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: 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.

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: 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.

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 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

302

201

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 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: 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.

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 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: 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.

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 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: 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.

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 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

302

201

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: 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.

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 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

304

201

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 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 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 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 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. 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%)	1.5 (1.4 to 2.4)	2.6 (1.4 to 3.9)

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 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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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 name

MedDRA

Dictionary version

22.1

Reporting group title

Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Reporting group description

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 3 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 1 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Escalation Cohort (MEDI4736 15 mg/kg Q3W)

Reporting group description

Reporting group title

Exploration Cohort (MEDI4736 20 mg/kg Q4W)

Reporting group description

Reporting group title

Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion Non-SCCHN Cohort HPV+ (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

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 UM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion STS Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Reporting group title

Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W)

Reporting group description

Escalation Cohort (MEDI4736 0.3 mg/kg Q2W)

Escalation Cohort (MEDI4736 0.1 mg/kg Q2W)

Escalation Cohort (MEDI4736 3 mg/kg Q2W)

Escalation Cohort (MEDI4736 1 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 Cohort HPV+ (MEDI4736 10 mg/kg Q2W)

Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W)

Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W)

Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion UM Cohort (MEDI4736 10 mg/kg Q2W)

Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W)

Expansion UC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion OC Cohort (MEDI4736 10 mg/kg Q2W)

Expansion STS 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

2 / 4 (50.00%)

1 / 4 (25.00%)

1 / 3 (33.33%)

3 / 6 (50.00%)

3 / 7 (42.86%)

13 / 21 (61.90%)

30 / 62 (48.39%)

16 / 22 (72.73%)

163 / 304 (53.62%)

7 / 21 (33.33%)

24 / 40 (60.00%)

26 / 51 (50.98%)

12 / 24 (50.00%)

20 / 40 (50.00%)

25 / 31 (80.65%)

9 / 20 (45.00%)

117 / 201 (58.21%)

26 / 47 (55.32%)

7 / 20 (35.00%)

31 / 62 (50.00%)

14 / 21 (66.67%)

7 / 10 (70.00%)

number of deaths (all causes)

208

128

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 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

1 / 22 (4.55%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

ADENOCARCINOMA PANCREAS

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

2 / 21 (9.52%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

3 / 31 (9.68%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 3

0 / 0

ANAL CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

3 / 22 (13.64%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

BLADDER CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

45 / 201 (22.39%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 50

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 42

0 / 0

BLADDER CANCER STAGE IV

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

1 / 201 (0.50%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

BLADDER TRANSITIONAL CELL CARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

4 / 201 (1.99%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 3

0 / 0

BREAST CANCER METASTATIC

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

1 / 40 (2.50%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CANCER PAIN

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

3 / 201 (1.49%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

CERVIX CARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

2 / 22 (9.09%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

CHOROID MELANOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

1 / 24 (4.17%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

COLON CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

2 / 62 (3.23%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

COLORECTAL ADENOCARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

1 / 62 (1.61%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLORECTAL CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

5 / 62 (8.06%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 5

0 / 0

ENDOMETRIAL CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

1 / 62 (1.61%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

GASTRIC CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

4 / 51 (7.84%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 4

0 / 0

GASTROOESOPHAGEAL CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 21 (4.76%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

1 / 51 (1.96%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

GLIOBLASTOMA MULTIFORME

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

2 / 20 (10.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

HEPATOCELLULAR CARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

7 / 40 (17.50%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 8

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 6

0 / 0

INTRAOCULAR MELANOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

2 / 24 (8.33%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

LUNG ADENOCARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

3 / 304 (0.99%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 3

0 / 0

LUNG CANCER METASTATIC

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

3 / 304 (0.99%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 3

0 / 0

LUNG NEOPLASM

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

1 / 304 (0.33%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

LUNG NEOPLASM MALIGNANT

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

13 / 304 (4.28%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

1 / 21 (4.76%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 14

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 12

0 / 0

0 / 1

0 / 0

MALIGNANT MELANOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

2 / 21 (9.52%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

MALIGNANT NEOPLASM OF RENAL PELVIS

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

1 / 201 (0.50%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

MALIGNANT PLEURAL EFFUSION

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

1 / 51 (1.96%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

METASTASES TO BLADDER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

1 / 201 (0.50%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

METASTATIC CARCINOMA OF THE BLADDER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

1 / 201 (0.50%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

METASTATIC GASTRIC CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

1 / 51 (1.96%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

METASTATIC MALIGNANT MELANOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

2 / 21 (9.52%)

0 / 40 (0.00%)

0 / 51 (0.00%)

1 / 24 (4.17%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

NASOPHARYNGEAL CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

4 / 10 (40.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

deaths causally related to treatment / all

0 / 0

0 / 4

NEOPLASM SWELLING

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

1 / 304 (0.33%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

NON-SMALL CELL LUNG CANCER

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

1 / 21 (4.76%)

0 / 62 (0.00%)

0 / 22 (0.00%)

47 / 304 (15.46%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 55

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 43

0 / 0

NON-SMALL CELL LUNG CANCER METASTATIC

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

1 / 304 (0.33%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

OESOPHAGEAL ADENOCARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

1 / 51 (1.96%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

OESOPHAGEAL CANCER METASTATIC

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

2 / 51 (3.92%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

OESOPHAGEAL CARCINOMA

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

3 / 51 (5.88%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 3

0 / 0

ONCOLOGIC COMPLICATION

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

1 / 62 (1.61%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

0 / 47 (0.00%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OVARIAN CANCER

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 21 (0.00%)

0 / 62 (0.00%)

0 / 22 (0.00%)

0 / 304 (0.00%)

0 / 21 (0.00%)

0 / 40 (0.00%)

0 / 51 (0.00%)

0 / 24 (0.00%)

0 / 40 (0.00%)

0 / 31 (0.00%)

0 / 20 (0.00%)

0 / 201 (0.00%)

7 / 47 (14.89%)

0 / 20 (0.00%)

0 / 62 (0.00%)

0 / 21 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 8

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 5

0 / 0

PANCREATIC CARCINOMA

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adverse events

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