Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44352   clinical trials with a EudraCT protocol, of which   7380   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1/2 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (ARTISTRY-2)

    Summary
    EudraCT number
    		 2019-002013-20
    Trial protocol
    		 GB   DE   ES   NL   FR  
    Global end of trial date
    01 Mar 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Jul 2025
    First version publication date
    17 Jul 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALKS4230-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03861793
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND: 128,159
    Sponsors
    Sponsor organisation name
    Mural Oncology, Inc
    Sponsor organisation address
    10 Earlsfort Terrace, Dublin, Ireland, D02 T380
    Public contact
    Study Director, Mural Oncology, Inc, +1 (781) 614-0100, clinicaltrials@muraloncology.com
    Scientific contact
    Study Director, Mural Oncology, Inc, +1 (781) 614-0100, clinicaltrials@muraloncology.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Mar 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Mar 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - To characterize the safety and tolerability and to identify the recommended Phase 2 dose (RP2D) of ALKS 4230 administered subcutaneously (SC) as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors (Phase 1) - To characterize the safety profile of SC ALKS 4230 at the RP2D in combination with pembrolizumab in subjects with advanced solid tumors (Phase 2) - To estimate the clinical activity of combination treatment with ALKS 4230 and pembrolizumab in terms of objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 separately for non–small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), squamous tumor agnostic, hepatocellular carcinoma (HCC), and small-cell lung cancer (SCLC) (Phase 2)
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles of Good Clinical Practice (GCP), according to the International Council on Harmonisation (ICH) Harmonised Tripartite Guideline, and in accordance with 21 CFR 312.120.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Mar 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    United States: 81
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    China: 1
    Country: Number of subjects enrolled
    Taiwan: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Worldwide total number of subjects
    116
    EEA total number of subjects
    16
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    69
    From 65 to 84 years
    47
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 50 investigative sites globally from 06 March 2019 to 01 March 2023.

    Pre-assignment
    Screening details
    		 Subjects were enrolled in this 2 phases study (Phase 1 and 2) to receive nemvaleukin alfa (ALKS 4230) either as monotherapy or in combination with pembrolizumab.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.3 milligram (mg) monotherapy, subcutaneous (SC) injection, every 7 days (Q7D). After 6 weeks of monotherapy, if tolerated, then pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation or study discontinuation or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, every 21 days (Q21D). After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion over 30 minutes in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Arm description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 10 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 2, Dose Expansion Phase, NSCLC
    Arm description
    		 Subjects with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 2, Dose Expansion Phase, SCCHN
    Arm description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer
    Arm description
    		 Subjects with gastric/gastroesophageal junction (GEJ) adenocarcinoma received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1
    Arm description
    		 Subjects with ovarian cancer (OC) in cohort 1 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Arm title
    		 Phase 2, Dose Expansion Phase, OC Cohort 2
    Arm description
    		 Subjects with ovarian cancer (OC) in cohort 2 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nemvaleukin Alfa
    Investigational medicinal product code
    Other name
    ALKS 4230
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nemvaleukin alfa administration via subcutaneous (SC) injection

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pembrolizumab administration via IV infusion.

    Number of subjects in period 1
    		Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Started
    7
    3
    7
    7
    8
    4
    4
    8
    9
    11
    10
    13
    17
    8
    Completed
    1
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Not completed
    6
    2
    7
    7
    8
    4
    2
    8
    9
    11
    10
    13
    17
    8
         Consent withdrawn by subject
    1
    1
    1
    -
    2
    -
    -
    2
    -
    -
    2
    1
    3
    2
         Adverse Event
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    2
         Death
    4
    1
    4
    7
    5
    2
    2
    3
    5
    5
    4
    10
    10
    1
         Lost to Follow-up
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
         Progressive Disease
    -
    -
    1
    -
    -
    -
    -
    1
    -
    -
    2
    -
    2
    -
         Unspecified
    1
    -
    1
    -
    1
    2
    -
    2
    3
    6
    2
    2
    2
    2
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.3 milligram (mg) monotherapy, subcutaneous (SC) injection, every 7 days (Q7D). After 6 weeks of monotherapy, if tolerated, then pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation or study discontinuation or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, every 21 days (Q21D). After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion over 30 minutes in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 10 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, NSCLC
    Reporting group description
    		 Subjects with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, SCCHN
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer
    Reporting group description
    		 Subjects with gastric/gastroesophageal junction (GEJ) adenocarcinoma received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 1 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, OC Cohort 2
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 2 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2 Total
    Number of subjects
    		 7 3 7 7 8 4 4 8 9 11 10 13 17 8 116
    Age categorical
    Units: Subjects
        In utero
    		 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
        Newborns (0-27 days)
    		 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
        Children (2-11 years)
    		 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
        Adults (18-64 years)
    		 3 3 4 4 6 2 3 4 4 5 3 10 12 6 69
        From 65-84 years
    		 4 0 3 3 2 2 1 4 5 6 7 3 5 2 47
        85 years and over
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 5 1 4 6 4 0 3 1 5 3 1 1 17 8 59
        Male
    		 2 2 3 1 4 4 1 7 4 8 9 12 0 0 57
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 1 0 1 0 1 0 0 0 0 0 3
        Not Hispanic or Latino
    		 7 3 7 7 7 4 3 8 8 11 10 13 17 8 113
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 0 0 0 2 5 0 3 1 0 11
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1
        Black or African American
    		 0 1 0 1 0 0 0 4 0 0 0 0 1 2 9
        White
    		 7 2 7 6 6 4 4 4 7 6 10 10 15 6 94
        More than one race
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.3 milligram (mg) monotherapy, subcutaneous (SC) injection, every 7 days (Q7D). After 6 weeks of monotherapy, if tolerated, then pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation or study discontinuation or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, every 21 days (Q21D). After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion over 30 minutes in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 10 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, NSCLC
    Reporting group description
    		 Subjects with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, SCCHN
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer
    Reporting group description
    		 Subjects with gastric/gastroesophageal junction (GEJ) adenocarcinoma received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 1 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, OC Cohort 2
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 2 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Primary: Phase 1 and 2: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [1]
    End point description
    TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. An AE was any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product. Safety population included all subjects who received any exposure to study drug (SC ALKS 4230 in Phase 1 and SC ALKS 4230 or pembrolizumab in Phase 2).
    End point type
    Primary
    End point timeframe
    From first dose of study drug until 30 days after last dose (up to 23.3 months for Phase 1 and up to 21.2 months for Phase 2)
    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 analysis was performed for this endpoint.
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    7
    3
    7
    7
    8
    4
    4
    8
    9
    11
    10
    13
    17
    8
    Units: Subjects
    7
    3
    7
    7
    8
    4
    4
    8
    9
    11
    10
    13
    17
    8
    No statistical analyses for this end point

    Primary: Phase 1 and 2: Number of Subjects With TEAEs by Severity Grading

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Number of Subjects With TEAEs by Severity Grading [2]
    End point description
    TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. Severity was graded according to the National Cancer Institute (NCI) CTCAE (version 4.03) where, Grade 1: Mild- asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate- minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. As planned, subjects experienced grade 3 or more were reported. Safety population included all subjects who received any exposure to study drug (SC ALKS 4230 in Phase 1 and SC ALKS 4230 or pembrolizumab in Phase 2).
    End point type
    Primary
    End point timeframe
    From first dose of study drug until 30 days after last dose (up to 23.3 months for Phase 1 and up to 21.2 months for Phase 2)
    Notes
    [2] - 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 analysis was performed for this endpoint.
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    7
    3
    7
    7
    8
    4
    4
    8
    9
    11
    10
    13
    17
    8
    Units: Subjects
    2
    2
    3
    7
    7
    3
    1
    3
    6
    7
    7
    10
    12
    7
    No statistical analyses for this end point

    Primary: Phase 2: Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    		 Close Top of page
    End point title
    		 Phase 2: Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [3] [4]
    End point description
    ORR rate was defined as the percentage of subjects with objective evidence of CR or PR based on RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The antitumor evaluable population consisted of subjects who complete 2 cycles of therapy and had at least one follow-up scan. Antitumor evaluable population included of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230.
    End point type
    Primary
    End point timeframe
    From first dose of study drug up to 20.2 months for Phase 2
    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 analysis was performed for this endpoint.
    [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: ORR was assessed in Part 1 arms only.
    End point values
    		 Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    10
    7
    13
    14
    6
    Units: percentage of subjects
        number (confidence interval 95%)
    10.0 (0.25 to 44.50)
    14.3 (0.36 to 57.87)
    0 (0.00 to 24.71)
    14.3 (1.78 to 42.81)
    0 (0.00 to 45.93)
    No statistical analyses for this end point

    Secondary: Phase 1: Number of Subjects With Dose-limiting Toxicities (DLTs)

    		 Close Top of page
    End point title
    		 Phase 1: Number of Subjects With Dose-limiting Toxicities (DLTs) [5]
    End point description
    DLT was defined by any of following events possibly, probably, or definitely related to ALKS 4230: Grade 4 neutrophil count decreased (neutropenia); Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; Thrombocytopenia; Any Grade 3 cardiac or central nervous system toxicity; Liver transaminase elevation higher than 8*upper limit of normal (ULN) or total bilirubin higher than 6*ULN; Grade 4 hypoalbuminemia; Fever more than (>) 40 degree Celsius (°C) sustained for >24 hours; Hypotension required the use of pressors or prolonged hospitalization (>48 hours) for hypotension requiring medical intervention; Grade 3 or higher electrolyte abnormalities; Increase in amylase or lipase; Grade 3 or higher nausea, vomiting, or diarrhea; Any other Grade 4 nonhematologic toxicity or any other Grade 3 nonhematologic toxicity; Any other toxicity or adverse event (AE) not defined above that resulted in subject removal from the study or discontinuation of dosing by the Investigator.
    End point type
    Secondary
    End point timeframe
    Phase 1: Cycle 1 Day 1 through Cycle 2 Day 15 (Cycle 1 length = 14 days; Cycle 2 length= 21 days)
    Notes
    [5] - 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: DLT was assessed in Part 1 arms only.
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Number of subjects analysed
    7
    3
    7
    7
    8
    4
    4
    8
    9
    Units: Subjects
    0
    0
    0
    0
    2
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Serum Concentrations of ALKS 4230 and Descriptive PK Parameters

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Serum Concentrations of ALKS 4230 and Descriptive PK Parameters
    End point description
    The PK population consists of all subjects who received at least 1 dose of ALKS 4230 and had at least 1 measurable serum concentration of ALKS 4230 at any scheduled PK time point. This outcome measure was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    0 [13]
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    0 [18]
    0 [19]
    Units: Micrograms per milliliter
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [6] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [7] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [8] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [9] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [10] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [11] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [12] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [13] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [14] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [15] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [16] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [17] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [18] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [19] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Presence of Anti-ALKS 4230 Antibodies in Serum

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Presence of Anti-ALKS 4230 Antibodies in Serum
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [20]
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    0 [29]
    0 [30]
    0 [31]
    0 [32]
    0 [33]
    Units: subjects
    Notes
    [20] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [21] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [22] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [23] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [24] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [25] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [26] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [27] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [28] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [29] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [30] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [31] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [32] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [33] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Numbers of Circulating CD8+ T Cells, Tregs, and NK Cells in Peripheral Blood

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Numbers of Circulating CD8+ T Cells, Tregs, and NK Cells in Peripheral Blood
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    0 [40]
    0 [41]
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    0 [46]
    0 [47]
    Units: subjects
    Notes
    [34] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [35] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [36] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [37] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [38] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [39] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [40] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [41] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [42] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [43] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [44] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [45] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [46] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [47] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Serum Concentrations of IL-6 and Other Cytokines

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Serum Concentrations of IL-6 and Other Cytokines
    End point description
    The PK population consists of all subjects who received at least 1 dose of ALKS 4230 and had at least 1 measurable serum concentration of ALKS 4230 at any scheduled PK time point. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [48]
    0 [49]
    0 [50]
    0 [51]
    0 [52]
    0 [53]
    0 [54]
    0 [55]
    0 [56]
    0 [57]
    0 [58]
    0 [59]
    0 [60]
    0 [61]
    Units: Micrograms per milliliter
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [48] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [49] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [50] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [51] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [52] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [53] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [54] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [55] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [56] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [57] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [58] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [59] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [60] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [61] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1: ORR Based on RECIST v1.1

    		 Close Top of page
    End point title
    		 Phase 1: ORR Based on RECIST v1.1 [62]
    End point description
    ORR rate was defined as the percentage of subjects with objective evidence of CR or PR based on RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1
    Notes
    [62] - 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: ORR was assessed in Part 1 arms only.
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Number of subjects analysed
    7
    3
    6
    6
    7
    3
    4
    8
    8
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0.00 to 40.96)
    0 (0.00 to 70.76)
    0 (0.00 to 45.93)
    0 (0.00 to 45.93)
    0 (0.00 to 40.96)
    0 (0.00 to 70.76)
    0 (0.00 to 60.24)
    1 (0.32 to 52.65)
    0 (0.00 to 36.94)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Disease Control Rate (DCR) Based on RECIST v1.1

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Disease Control Rate (DCR) Based on RECIST v1.1
    End point description
    Disease control rate was defined as the percentage of participants with objective evidence of CR, PR, or SD based on RECIST v.1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    7
    3
    6
    6
    7
    3
    4
    8
    8
    10
    7
    13
    14
    6
    Units: percentage of subjects
        number (confidence interval 95%)
    14.3 (0.36 to 57.87)
    33.3 (0.84 to 90.57)
    0 (0.00 to 45.93)
    33.3 (4.33 to 77.72)
    0 (0.00 to 40.96)
    33.3 (0.84 to 90.57)
    0 (0.00 to 60.24)
    12.5 (0.32 to 52.65)
    0 (0.00 to 36.94)
    40.0 (12.16 to 73.76)
    28.6 (3.67 to 70.96)
    30.8 (9.09 to 61.43)
    28.6 (8.39 to 58.10)
    16.7 (0.42 to 64.12)
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Duration of Response (DOR) Based on RECIST v1.1

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Duration of Response (DOR) Based on RECIST v1.1
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to lack of responses (CR or PR), data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause (up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2)
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [63]
    0 [64]
    0 [65]
    0 [66]
    0 [67]
    0 [68]
    0 [69]
    0 [70]
    0 [71]
    0 [72]
    0 [73]
    0 [74]
    0 [75]
    0 [76]
    Units: days
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [63] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [64] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [65] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [66] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [67] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [68] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [69] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [70] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [71] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [72] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [73] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [74] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [75] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [76] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Time to Response (TTR) Based on RECIST v1.1

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Time to Response (TTR) Based on RECIST v1.1
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to lack of responses (CR or PR), data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [77]
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    0 [82]
    0 [83]
    0 [84]
    0 [85]
    0 [86]
    0 [87]
    0 [88]
    0 [89]
    0 [90]
    Units: days
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [77] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [78] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [79] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [80] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [81] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [82] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [83] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [84] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [85] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [86] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [87] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [88] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [89] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [90] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Progression Free Survival (PFS) Based on RECIST v1.1

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Progression Free Survival (PFS) Based on RECIST v1.1
    End point description
    Progression-free survival was defined as the time from the first dose of nemvaleukin to the first documentation of objective tumor progression or death due to any cause. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to the first documentation of objective tumor progression or death due to any cause (up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2)
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [91]
    0 [92]
    0 [93]
    0 [94]
    0 [95]
    0 [96]
    0 [97]
    0 [98]
    0 [99]
    10
    7
    13
    14
    6
    Units: weeks
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    11.71 (4.57 to 99999)
    14.14 (5.29 to 45.43)
    6.14 (5.29 to 22.57)
    8.71 (6.00 to 19.43)
    14.29 (4.29 to 16.00)
    Notes
    [91] - no data
    [92] - no data
    [93] - no data
    [94] - no data
    [95] - no data
    [96] - no data
    [97] - no data
    [98] - no data
    [99] - no data
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Immune ORR (iORR) Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Immune ORR (iORR) Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [100]
    0 [101]
    0 [102]
    0 [103]
    0 [104]
    0 [105]
    0 [106]
    0 [107]
    0 [108]
    0 [109]
    0 [110]
    0 [111]
    0 [112]
    0 [113]
    Units: percentage of subjects
    Notes
    [100] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [101] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [102] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [103] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [104] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [105] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [106] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [107] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [108] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [109] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [110] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [111] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [112] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [113] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Immune DCR (iDCR) Based on iRECIST

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Immune DCR (iDCR) Based on iRECIST
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [114]
    0 [115]
    0 [116]
    0 [117]
    0 [118]
    0 [119]
    0 [120]
    0 [121]
    0 [122]
    0 [123]
    0 [124]
    0 [125]
    0 [126]
    0 [127]
    Units: percentage of subjects
    Notes
    [114] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [115] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [116] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [117] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [118] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [119] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [120] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [121] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [122] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [123] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [124] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [125] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [126] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [127] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Immune DOR (iDOR) Based on iRECIST

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Immune DOR (iDOR) Based on iRECIST
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause (up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2)
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [128]
    0 [129]
    0 [130]
    0 [131]
    0 [132]
    0 [133]
    0 [134]
    0 [135]
    0 [136]
    0 [137]
    0 [138]
    0 [139]
    0 [140]
    0 [141]
    Units: days
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [128] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [129] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [130] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [131] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [132] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [133] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [134] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [135] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [136] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [137] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [138] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [139] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [140] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [141] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 1 and 2: Immune PFS (iPFS) Based on iRECIST

    		 Close Top of page
    End point title
    		 Phase 1 and 2: Immune PFS (iPFS) Based on iRECIST
    End point description
    The efficacy population will consist of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230. This endpoint was planned but due to a decision to prioritize less frequent IV dosing, data are not available, and no analyses were performed.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to the first documentation of objective tumor progression or death due to any cause (up to 22.3 months for Phase 1 and up to 20.2 months for Phase 2)
    End point values
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    0 [142]
    0 [143]
    0 [144]
    0 [145]
    0 [146]
    0 [147]
    0 [148]
    0 [149]
    0 [150]
    0 [151]
    0 [152]
    0 [153]
    0 [154]
    0 [155]
    Units: percentage of subjects
    Notes
    [142] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [143] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [144] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [145] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [146] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [147] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [148] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [149] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [150] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [151] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [152] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [153] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [154] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    [155] - Due to a decision to prioritize less frequent IV dosing, no analyses were performed.
    No statistical analyses for this end point

    Secondary: Phase 2: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Phase 2: Overall Survival (OS) [156]
    End point description
    Overall survival was defined as the time from the first dose to the date of death due to any cause. For participants without documentation of death, overall survival was censored on the last date the participants were known to be alive. Antitumor evaluable population included of all subjects who had at least one assessment of tumor size after exposure to ALKS 4230.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until 30 days after last dose (up to 21.2 months for Phase 2)
    Notes
    [156] - 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: OS was assessed in Part 1 arms only.
    End point values
    		 Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Number of subjects analysed
    10
    7
    13
    14
    6
    Units: weeks
        median (confidence interval 95%)
    99999 (5.14 to 99999)
    99999 (5.86 to 99999)
    24.43 (8.43 to 40.57)
    19.43 (8.86 to 99999)
    99999 (7.00 to 99999)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 30 days after last dose (up to 23.3 months for Phase 1 and up to 21.2 months for Phase 2)
    Adverse event reporting additional description
    Safety population included all subjects who received any exposure to study drug (SC ALKS 4230 in Phase 1 and SC ALKS 4230 or pembrolizumab in Phase 2).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25
    Reporting groups
    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.3 milligram (mg) monotherapy, subcutaneous (SC) injection, every 7 days (Q7D). After 6 weeks of monotherapy, if tolerated, then pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation or study discontinuation or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 0.6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q7D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 1 mg monotherapy, SC injection, every 21 days (Q21D). After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 3 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 6 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion over 30 minutes in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D
    Reporting group description
    		 Subjects with advanced solid tumors received nemvaleukin alfa 10 mg monotherapy, SC injection, Q21D. After 6 weeks of monotherapy, if tolerated, pembrolizumab was added as an intravenous infusion in a dose of 200 mg every 3 weeks with the ALKS 4230 regimen. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, NSCLC
    Reporting group description
    		 Subjects with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, SCCHN
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer
    Reporting group description
    		 Subjects with gastric/gastroesophageal junction (GEJ) adenocarcinoma received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 1 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Reporting group title
    Phase 2, Dose Expansion Phase, OC Cohort 2
    Reporting group description
    		 Subjects with ovarian cancer (OC) in cohort 2 received nemvaleukin alfa 3 mg monotherapy, SC injection, Q7D with pembrolizumab 200 mg, intravenous infusion, Q21D. Subjects who received combination treatment with SC ALKS 4230 and pembrolizumab continued to receive treatment with the study regimen for up to 2 years following initiation of combination treatment, as long as the subject derives clinical benefit or until the occurrence of any of the other criteria for treatment discontinuation, study discontinuation, or withdrawal. Subjects might continue ALKS 4230 as monotherapy after confirmation with the Sponsor if they appeared to be deriving clinical benefit.

    Serious adverse events
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    3 / 7 (42.86%)
    4 / 7 (57.14%)
    4 / 8 (50.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    3 / 11 (27.27%)
    4 / 10 (40.00%)
    3 / 13 (23.08%)
    9 / 17 (52.94%)
    4 / 8 (50.00%)
         number of deaths (all causes)
    4
    1
    4
    7
    5
    2
    2
    3
    5
    5
    4
    10
    10
    1
         number of deaths resulting from adverse events
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    2
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour flare
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Depressed level of consciousness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Small intestinal obstruction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Swollen tongue
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 0.6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q7D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 1mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 3mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 6mg Q21D Phase 1, Dose Escalation Phase: Nemvaleukin Alfa 10mg Q21D Phase 2, Dose Expansion Phase, NSCLC Phase 2, Dose Expansion Phase, SCCHN Phase 2, Dose Expansion Phase, Gastric/GEJ Cancer Phase 2, Dose Expansion Phase, Ovarian Cancer Cohort 1 Phase 2, Dose Expansion Phase, OC Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    3 / 3 (100.00%)
    7 / 7 (100.00%)
    7 / 7 (100.00%)
    8 / 8 (100.00%)
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    8 / 8 (100.00%)
    9 / 9 (100.00%)
    11 / 11 (100.00%)
    10 / 10 (100.00%)
    13 / 13 (100.00%)
    17 / 17 (100.00%)
    8 / 8 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    3
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    3 / 9 (33.33%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    4 / 17 (23.53%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    0
    3
    3
    0
    1
    1
    6
    0
    Hypertension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    3
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    5 / 7 (71.43%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    5 / 7 (71.43%)
    5 / 8 (62.50%)
    0 / 4 (0.00%)
    4 / 4 (100.00%)
    4 / 8 (50.00%)
    7 / 9 (77.78%)
    8 / 11 (72.73%)
    6 / 10 (60.00%)
    6 / 13 (46.15%)
    8 / 17 (47.06%)
    2 / 8 (25.00%)
         occurrences all number
    12
    0
    2
    5
    5
    0
    6
    6
    19
    45
    26
    25
    12
    2
    Fatigue
         subjects affected / exposed
    5 / 7 (71.43%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    3 / 7 (42.86%)
    6 / 8 (75.00%)
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    4 / 9 (44.44%)
    1 / 11 (9.09%)
    6 / 10 (60.00%)
    4 / 13 (30.77%)
    9 / 17 (52.94%)
    0 / 8 (0.00%)
         occurrences all number
    15
    2
    4
    5
    7
    1
    2
    3
    7
    1
    26
    5
    18
    0
    Chills
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    5 / 7 (71.43%)
    5 / 8 (62.50%)
    0 / 4 (0.00%)
    3 / 4 (75.00%)
    1 / 8 (12.50%)
    7 / 9 (77.78%)
    4 / 11 (36.36%)
    3 / 10 (30.00%)
    3 / 13 (23.08%)
    9 / 17 (52.94%)
    0 / 8 (0.00%)
         occurrences all number
    13
    0
    2
    9
    8
    0
    3
    1
    14
    11
    3
    8
    18
    0
    Injection site erythema
         subjects affected / exposed
    5 / 7 (71.43%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    3 / 8 (37.50%)
    2 / 4 (50.00%)
    3 / 4 (75.00%)
    4 / 8 (50.00%)
    4 / 9 (44.44%)
    4 / 11 (36.36%)
    2 / 10 (20.00%)
    3 / 13 (23.08%)
    3 / 17 (17.65%)
    1 / 8 (12.50%)
         occurrences all number
    10
    0
    2
    2
    3
    2
    5
    4
    5
    14
    3
    5
    12
    2
    Injection site reaction
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    2 / 7 (28.57%)
    5 / 7 (71.43%)
    4 / 8 (50.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 9 (33.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    1
    2
    14
    16
    1
    2
    2
    5
    0
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    4 / 7 (57.14%)
    1 / 3 (33.33%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    4 / 8 (50.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    4
    4
    2
    0
    0
    1
    1
    5
    1
    0
    1
    1
    6
    0
    Injection site pain
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    2 / 8 (25.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 9 (22.22%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    3 / 13 (23.08%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    4
    0
    1
    2
    4
    1
    0
    3
    2
    7
    0
    3
    2
    0
    Injection site swelling
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    2 / 8 (25.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    1
    2
    2
    0
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    2 / 8 (25.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    1 / 8 (12.50%)
         occurrences all number
    2
    1
    0
    1
    2
    1
    0
    0
    1
    2
    3
    1
    3
    1
    Pain
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    12
    0
    1
    0
    0
    0
    0
    0
    2
    3
    0
    1
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    4 / 11 (36.36%)
    1 / 10 (10.00%)
    3 / 13 (23.08%)
    4 / 17 (23.53%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    0
    11
    1
    5
    4
    0
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Injection site oedema
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    1
    0
    1
    1
    1
    4
    0
    Nodule
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Physical deconditioning
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    0
    1
    0
    0
    Injection site rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    1 / 7 (14.29%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    1 / 11 (9.09%)
    3 / 10 (30.00%)
    1 / 13 (7.69%)
    3 / 17 (17.65%)
    0 / 8 (0.00%)
         occurrences all number
    2
    3
    1
    1
    1
    0
    0
    0
    1
    1
    4
    1
    4
    0
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    4 / 17 (23.53%)
    1 / 8 (12.50%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    0
    0
    1
    3
    1
    1
    5
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    3 / 11 (27.27%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    3 / 7 (42.86%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
    2 / 9 (22.22%)
    6 / 11 (54.55%)
    3 / 10 (30.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    1
    5
    0
    0
    0
    4
    2
    8
    4
    1
    2
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    4 / 7 (57.14%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 9 (22.22%)
    6 / 11 (54.55%)
    2 / 10 (20.00%)
    2 / 13 (15.38%)
    4 / 17 (23.53%)
    4 / 8 (50.00%)
         occurrences all number
    0
    0
    1
    5
    0
    0
    0
    3
    2
    8
    2
    3
    5
    6
    Blood creatinine increased
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    3 / 9 (33.33%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    6 / 17 (35.29%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    0
    1
    1
    7
    2
    1
    3
    12
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    3 / 11 (27.27%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    2 / 17 (11.76%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    1
    1
    5
    0
    0
    2
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    1
    1
    0
    0
    1
    1
    Blood urea increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    Oxygen saturation decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    1
    1
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    2 / 13 (15.38%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    6
    3
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    2
    4
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    3 / 13 (23.08%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    4
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    2
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    6
    1
    0
    Flank pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    1 / 17 (5.88%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    2
    0
    0
    1
    1
    3
    Fall
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 9 (33.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    2
    1
    0
    0
    0
    3
    0
    0
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 13 (15.38%)
    3 / 17 (17.65%)
    1 / 8 (12.50%)
         occurrences all number
    1
    0
    0
    0
    3
    0
    0
    2
    2
    0
    1
    3
    3
    1
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    4 / 8 (50.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 9 (22.22%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences all number
    1
    1
    1
    2
    7
    0
    1
    1
    3
    2
    0
    0
    1
    2
    Neuropathy peripheral
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    4
    0
    1
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    4 / 7 (57.14%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    4 / 8 (50.00%)
    1 / 9 (11.11%)
    3 / 11 (27.27%)
    2 / 10 (20.00%)
    3 / 13 (23.08%)
    3 / 17 (17.65%)
    1 / 8 (12.50%)
         occurrences all number
    4
    0
    2
    4
    0
    2
    0
    6
    2
    5
    3
    4
    10
    1
    Lymphopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    4 / 7 (57.14%)
    3 / 7 (42.86%)
    2 / 8 (25.00%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    6
    4
    2
    2
    1
    0
    5
    1
    0
    1
    1
    0
    Neutropenia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    0
    4
    2
    0
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    3 / 7 (42.86%)
    4 / 7 (57.14%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
    5 / 9 (55.56%)
    4 / 11 (36.36%)
    4 / 10 (40.00%)
    5 / 13 (38.46%)
    9 / 17 (52.94%)
    3 / 8 (37.50%)
         occurrences all number
    11
    0
    4
    4
    2
    0
    2
    4
    9
    6
    11
    7
    13
    3
    Vomiting
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 3 (0.00%)
    2 / 7 (28.57%)
    2 / 7 (28.57%)
    5 / 8 (62.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    5 / 9 (55.56%)
    3 / 11 (27.27%)
    4 / 10 (40.00%)
    2 / 13 (15.38%)
    9 / 17 (52.94%)
    1 / 8 (12.50%)
         occurrences all number
    7
    0
    2
    2
    7
    0
    0
    3
    7
    4
    8
    2
    16
    1
    Diarrhoea
         subjects affected / exposed
    4 / 7 (57.14%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    2 / 9 (22.22%)
    2 / 11 (18.18%)
    2 / 10 (20.00%)
    2 / 13 (15.38%)
    6 / 17 (35.29%)
    0 / 8 (0.00%)
         occurrences all number
    9
    1
    2
    0
    2
    0
    1
    1
    3
    4
    2
    3
    9
    0
    Abdominal pain
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    3 / 7 (42.86%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    2 / 13 (15.38%)
    7 / 17 (41.18%)
    1 / 8 (12.50%)
         occurrences all number
    4
    2
    3
    1
    0
    0
    0
    0
    1
    0
    2
    3
    8
    1
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 3 (66.67%)
    2 / 7 (28.57%)
    3 / 7 (42.86%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    6 / 13 (46.15%)
    2 / 17 (11.76%)
    1 / 8 (12.50%)
         occurrences all number
    1
    2
    2
    4
    1
    0
    0
    0
    0
    2
    2
    6
    2
    1
    Abdominal distension
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    2 / 7 (28.57%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Gastritis
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    3 / 17 (17.65%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    3
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    2 / 7 (28.57%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    3 / 13 (23.08%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    2
    0
    0
    2
    1
    3
    2
    1
    1
    3
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    3
    0
    0
    0
    1
    1
    0
    0
    1
    1
    3
    5
    1
    0
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Rash pruritic
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    4
    0
    0
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    7
    0
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    2
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    2 / 9 (22.22%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    3 / 13 (23.08%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    4
    1
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    2 / 17 (11.76%)
    0 / 8 (0.00%)
         occurrences all number
    3
    1
    0
    1
    1
    2
    3
    0
    0
    0
    1
    1
    2
    0
    Arthralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    2 / 9 (22.22%)
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    2 / 13 (15.38%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    4
    1
    0
    2
    2
    1
    0
    2
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
    Myalgia
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    1
    0
    1
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 7 (42.86%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    4
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
    3 / 9 (33.33%)
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    5 / 17 (29.41%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    2
    5
    1
    1
    0
    5
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    4
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    2 / 7 (28.57%)
    3 / 8 (37.50%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
    3 / 9 (33.33%)
    8 / 11 (72.73%)
    2 / 10 (20.00%)
    4 / 13 (30.77%)
    5 / 17 (29.41%)
    1 / 8 (12.50%)
         occurrences all number
    1
    1
    1
    2
    3
    2
    1
    2
    5
    13
    2
    5
    6
    1
    Dehydration
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 3 (33.33%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    3 / 9 (33.33%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    5 / 17 (29.41%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    0
    0
    0
    8
    0
    0
    0
    7
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    2 / 8 (25.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 13 (0.00%)
    4 / 17 (23.53%)
    2 / 8 (25.00%)
         occurrences all number
    2
    1
    3
    0
    2
    0
    0
    1
    1
    0
    2
    0
    4
    2
    Hypercalcaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 13 (0.00%)
    1 / 17 (5.88%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    2
    1
    0
    4
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    1 / 9 (11.11%)
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 13 (7.69%)
    0 / 17 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    3
    0
    1
    0
    0
    0
    0
    0
    1
    0
    1
    2
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 3 (33.33%)
    1 / 7 (14.29%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    0 / 13 (0.00%)
    4 / 17 (23.53%)
    2 / 8 (25.00%)
         occurrences all number
    0
    1
    4
    0
    1
    0
    0
    0
    0
    2
    1
    0
    4
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
    0 / 9 (0.00%)
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 13 (7.69%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    3
    1
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 3 (0.00%)
    0 / 7 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
    0 / 9 (0.00%)
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 13 (0.00%)
    0 / 17 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    1
    0
    2
    0
    0
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Aug 14 02:16:18 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA