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   43871   clinical trials with a EudraCT protocol, of which   7290   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 Dose-optimization, Exploratory Phase Ib/II Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143, When Given in Combination With the Anti-PD-1 Antibody Nivolumab in Patients With Specific Solid Tumors Who Have Progressed During or Immediately After Anti-PD-1/PD-L1 Treatment

    Summary
    EudraCT number
    		 2018-003546-16
    Trial protocol
    		 ES  
    Global end of trial date
    06 Apr 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    19 Oct 2023
    First version publication date
    21 Apr 2023
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Update to the description of endpoints #1, #5, #13, and title of endpoint #5, #24, #25, #26. Updated the endpoints #4, #6 #7, #8, #15, #17, #27. Updates to the timeframe of endpoints #18 to #26 and adverse event reporting time frame.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Debio 1143-106
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04122625
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Debiopharm International S.A.
    Sponsor organisation address
    Case postale 5911, Chemin Messidor 5-7, Lausanne, Switzerland, 1002
    Public contact
    Clinical department, Debiopharm International SA, +34 91756 78 25, ClinicalTrials@debiopharm.com
    Scientific contact
    Clinical department, Debiopharm International SA, +34 91756 78 25, ClinicalTrials@debiopharm.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
    06 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part A (dose optimisation)- To determine the recommended phase 2 dose (RP2D) taking into account dose-limiting toxicity (DLT/s) in Cycle 1, overall safety/tolerability and pharmacokinetic (PK), by optimizing doses of Debio 1143 when combined with the standard dose of nivolumab, as well as treatment compliance in subjects with advanced solid malignancies who failed prior systemic standard treatments. Part B (basket trial)- To evaluate the preliminary antitumor activity of Debio 1143 at the RP2D in combination with nivolumab, overall and in each cohort.
    Protection of trial subjects
    Written approval of the study protocol and the informed consent was obtained from the independent ethics committee (IEC), prior to initiation of the study. The study was conducted in accordance with local regulations, Good Clinical Practice (GCP), International Council for Harmonisation (ICH) notes for GCP (ICH/CPMP/135/95), and ethical principles that have their origin in the Declaration of Helsinki and its amendments.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 26
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    United States: 9
    Worldwide total number of subjects
    46
    EEA total number of subjects
    37
    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)
    23
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects took part at 24 investigational sites in the United States, Spain, and France from 26 April 2019 to 6 April 2022.

    Pre-assignment
    Screening details
    		 A total of 46 subjects were enrolled in this study, 11 subjects with advanced solid malignancies into Part A of study who failed prior systemic standard treatments and 35 subjects into Part B of the study. Part B of the study was started after the completion of Part A and did not include any subjects from Part A.

    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
    		 Part A: Debio 1143 150 mg + Nivolumab
    Arm description
    		 Subjects received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg administered once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Arm title
    		 Part A: Debio 1143 200 mg + Nivolumab
    Arm description
    		 Subjects received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Arm title
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab
    Arm description
    		 Subjects with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once on Days 1 to 28 in each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Arm title
    		 Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab
    Arm description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once on Days 1 to 28 in each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Arm title
    		 Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab
    Arm description
    		 Subjects with gastrointestinal (GI) cancers received Debio 1143, 200 mg capsules orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once on Days 1 to 28 in each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Arm title
    		 PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Arm description
    		 Subjects with gynaecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1143
    Investigational medicinal product code
    Other name
    Xevinapant
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once on Days 1 to 28 in each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    240 mg administered once on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Number of subjects in period 1
    		Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Started
    3
    8
    8
    8
    8
    11
    Completed
    1
    4
    2
    0
    0
    4
    Not completed
    2
    4
    6
    8
    8
    7
         Death
    2
    4
    5
    7
    6
    7
         Lost to follow-up
    -
    -
    1
    1
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part A: Debio 1143 150 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part A: Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with gastrointestinal (GI) cancers received Debio 1143, 200 mg capsules orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Reporting group description
    		 Subjects with gynaecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab Total
    Number of subjects
    		 3 8 8 8 8 11 46
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 71.0 ( 11.36 ) 55.5 ( 16.70 ) 65.5 ( 5.37 ) 61.6 ( 7.42 ) 63.9 ( 14.17 ) 64.8 ( 10.02 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1 1 4 1 3 11 21
        Male
    		 2 7 4 7 5 0 25
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0 1 0 0 0 1
        Not Hispanic or Latino
    		 3 7 5 6 7 6 34
        Unknown
    		 0 1 2 2 1 5 11
    Race
    Units: Subjects
        White
    		 3 7 6 5 7 6 34
        Other
    		 0 0 0 1 0 0 1
        Unknown
    		 0 1 2 2 1 5 11

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Part A: Debio 1143 150 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part A: Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with gastrointestinal (GI) cancers received Debio 1143, 200 mg capsules orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Reporting group description
    		 Subjects with gynaecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Primary: Part A: Number of Subjects With Dose-Limiting Toxicities (DLTs)

    		 Close Top of page
    End point title
    		 Part A: Number of Subjects With Dose-Limiting Toxicities (DLTs) [1] [2]
    End point description
    DLT: any of following treatment-emergent adverse events(TEAEs) as per NCI CTCAE Grade V5.0 Criteria(Grades 1=mild, 2=moderate, 3=severe and 4 or 5= life-threatening/fatal outcomes) which are related to combination treatment and occurring in Cycle[C]1(1 Cycle=28 days):Any Grade(Gr)4/5 hematologic toxicity,clinical/laboratory non-hematologic toxicity;febrile neutropenia any grade,Gr3 thrombocytopenia if associated with bleeding/requiring platelet transfusion;Gr2;Gr3 and any other Gr3 non-hematologic,treatment-related clinical toxicity lasting ≥3 days;delay of>2 weeks due to drug-related toxicity in initiating C2;unable to complete at least 70%of the scheduled treatment,i.e.>6 Debio 1143 skipped doses in C1 due to treatment-related toxicity;required dose reduction in C1 or on C2 Day1/requirement for treatment withdrawal due to treatment-related toxicity (even if not meeting other DLT criteria).RP2D population=subjects who received ≥70%of Debio 1143 and ≥1 nivolumab dose as planned in C1.
    End point type
    Primary
    End point timeframe
    Part A: Cycle 1 (28 days)
    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: Only descriptive statistical analysis was planned to be reported for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    6
    Units: subjects
    0
    0
    No statistical analyses for this end point

    Primary: Part B: Confirmed Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Part B: Confirmed Objective Response Rate (ORR) [3] [4]
    End point description
    ORR was determined per response evaluation criteria in solid tumors (RECIST) v1.1 and/or gynaecologic cancer intergroup (GCIG) criteria (for Cohort 4). ORR was calculated as the percentage of subjects with a confirmed objective response. A confirmed objective response was derived as any partial response (PR) or complete response (CR) recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to <10 millimetres (mm). PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Safety analysis set included all enrolled subjects who received at least one dose of any study drug in Part B.
    End point type
    Primary
    End point timeframe
    Part B: From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.05 years)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistical analysis was planned to be reported 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: This endpoint was applicable only for Part B arm groups of the study.
    End point values
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    8
    8
    8
    11
    Units: percentage of subjects
        number (confidence interval 95%)
    0.0 (0 to 37)
    0.0 (0 to 37)
    0.0 (0 to 37)
    9.1 (0 to 41)
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Including Laboratory Abnormalities Reported as TEAEs, and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Including Laboratory Abnormalities Reported as TEAEs, and Serious Adverse Events (SAEs)
    End point description
    An adverse event(AE) is any untoward medical occurrence in a clinical trial subject administered a medicinal product that does not necessarily have a causal relationship with this treatment. TEAE is any new,related or non-related,undesirable medical occurrence or change of an existing condition in a subject that occurs during the TE period,starting/ worsening on or after the first study drug administration and up to 5 months after last nivolumab infusion,or the earliest date of new anticancer therapy –1 day,whichever occurs first.An SAE is defined as any untoward medical occurrence that at any dose results in death;is life-threatening(i.e.,puts the subject at immediate risk of death);requires inpatient hospitalization or prolongation of existing hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect,or is otherwise medically significant.Safety analysis set= all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy –1 day, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: subjects
        TEAEs
    3
    8
    8
    8
    8
    11
        SAEs
    0
    8
    0
    6
    5
    5
    No statistical analyses for this end point

    Secondary: Parts A and B: Change From Baseline in Weight

    		 Close Top of page
    End point title
    		 Parts A and B: Change From Baseline in Weight
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug. Number of subjects analysed indicates the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    4
    7
    3
    4
    8
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    -5.57 ( 5.705 )
    -10.00 ( 9.416 )
    -4.33 ( 3.888 )
    -4.00 ( 6.557 )
    -0.80 ( 5.415 )
    -1.11 ( 1.680 )
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With Markedly Abnormal Change From Baseline in Vital Signs

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With Markedly Abnormal Change From Baseline in Vital Signs
    End point description
    Vital sign parameters assessed comprise of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Markedly abnormal criteria for vital signs include SBP [millimeters of mercury (mmHg)]: ≤ 90 mmHg OR change from baseline ≤ -20 mmHg, ≥ 140 mmHg OR change from baseline ≥ 20 mmHg; DBP (mmHg): ≤ 60 mmHg OR change from baseline ≤ -20 mmHg, ≥ 90 mmHg OR change from baseline ≥ 20 mmHg; Heart rate [beats per minute (bpm)]: ≤ 50 bpm OR change from baseline ≤ -20 bpm, ≥ 100 bpm OR change from baseline ≥ 20 bpm. Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: subjects
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With Change From Baseline in Temperature Reported as TEAEs

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With Change From Baseline in Temperature Reported as TEAEs
    End point description
    Change from baseline in temperature reported as TEAEs included pyrexia. A TEAE is any new, related or non-related, undesirable medical occurrence or change of an existing condition in a subject that occurs during the treatment-emergent period, starting or worsening on or after the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy - 1 day, whichever occurs first. Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: subjects
    0
    2
    1
    1
    0
    3
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With Markedly Abnormal Change From Baseline in Electrocardiogram (ECG) Readings

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With Markedly Abnormal Change From Baseline in Electrocardiogram (ECG) Readings
    End point description
    ECG parameters comprised of PR interval(Int) [millisecond(msec)],QRS Int(msec),QT Int(msec),QTcB Int(msec),QTcF Int(msec),heart rate(HR)[bpm],RR Int(msec),derived HR(msec),calculated as 60000/RR Int[for data checking only:should be within 5% of HR].Marked abnormal criteria for ECG parameters=absolute values QRS Int:<50 msec,>110 msec;absolute values for QT Int,QTcB Int:>450 msec,>480 msec,>500 msec,QTcF:>480 msec,>500 msec;change from baseline values for QTcB Int,and QTcF:>30 msec increase from baseline,>60 msec increase from baseline.Data for highest on-treatment change from baseline per markedly abnormal criteria for ECG parameters are reported. On-treatment=time between first and last administration of any study drug.Subjects with ≥1 markedly abnormal change from baseline value in above categories are reported.Safety analysis set=all subjects who were enrolled and received ≥1 dose of any study drug.Number of subjects analysed indicates the number of subjects available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    2
    8
    8
    8
    8
    11
    Units: subjects
        QRS duration: >110 msec
    0
    3
    1
    1
    2
    0
        QT Interval: >450 msec
    0
    1
    2
    1
    3
    0
        QT Interval: >480 msec
    0
    1
    0
    0
    0
    0
        QTcB Interval: >450 msec
    2
    2
    3
    5
    1
    5
        QTcB Interval: >480 msec
    0
    0
    0
    0
    1
    1
        QTcB Interval: >500 msec
    0
    1
    0
    1
    0
    0
        QTcB Interval: >30 msec increase from baseline
    0
    4
    3
    5
    3
    6
        QTcB Interval: >60 msec increase from baseline
    0
    0
    0
    1
    0
    0
        QTcB Interval: >30/>60msec increase from baseline
    0
    4
    3
    6
    3
    6
        QTcF Interval: >480 msec
    0
    1
    0
    0
    0
    0
        QTcF Interval: >500 msec
    0
    0
    0
    1
    0
    0
        QTcF Interval: >30 msec increase from baseline
    0
    1
    2
    3
    1
    4
        QTcF Interval: >60 msec increase from baseline
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With Shift From Baseline to Worst On-Treatment Value in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With Shift From Baseline to Worst On-Treatment Value in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)
    End point description
    The ECOG-PS was used to assess the effect of disease progression on subjects’ daily activities. ECOG-PS is graded as follows: Grade 0 - fully active, able to carry on all pre-disease performance without restriction; Grade 1 - restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2 - ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; Grade 3 - capable of only limited self-care, confined to bed or chair for more than 50% of waking hours; Grade 4 - completely disabled, cannot carry on any self-care, totally confined to bed or chair; Grade 5 - dead. Shift values from baseline grade to worst on-treatment grade and missing values were reported. Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: subjects
        Shift From Grade 0 to Grade 0
    1
    3
    0
    2
    1
    1
        Shift From Grade 0 to Grade 1
    0
    2
    3
    0
    2
    4
        Shift From Grade 0 to Grade 2
    0
    1
    2
    0
    1
    0
        Shift From Grade 0 to Grade 3
    0
    0
    0
    0
    1
    0
        Shift From Grade 1 to Grade 1
    2
    1
    2
    3
    2
    5
        Shift From Grade 1 to Grade 2
    0
    1
    1
    1
    1
    0
        Shift From Grade 1 to Grade 3
    0
    0
    0
    2
    0
    0
        Missing
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Parts A and B: Number of Subjects With TEAEs Including Laboratory Abnormalities Leading to Treatment Discontinuations and Dose Modifications

    		 Close Top of page
    End point title
    		 Parts A and B: Number of Subjects With TEAEs Including Laboratory Abnormalities Leading to Treatment Discontinuations and Dose Modifications
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy –1 day, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: subjects
        TEAEs Leading to Discontinuation of Debio 1143
    1
    1
    0
    3
    1
    2
        TEAEs Leading to Discontinuation of Nivolumab
    1
    1
    0
    3
    1
    2
        TEAEs Leading to Dose Modification of Debio 1143
    2
    5
    5
    5
    3
    4
        TEAEs Leading to Dose Modification of Nivolumab
    2
    6
    4
    5
    1
    4
    No statistical analyses for this end point

    Secondary: Part A: Confirmed Objective Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Part A: Confirmed Objective Response Rate (ORR) [5]
    End point description
    ORR was determined per RECIST v1.1. ORR was calculated as the percentage of subjects with a confirmed objective response. A confirmed objective response is a confirmed best overall response of PR or CR recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to <10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Safety analysis set included all enrolled subjects who received at least one dose of any study drug in Part A.
    End point type
    Secondary
    End point timeframe
    Part A: From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.08 years)
    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: Only descriptive statistical analysis was planned to be reported for this endpoint.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    8
    Units: percentage of subjects
        number (not applicable)
    0.0
    12.5
    No statistical analyses for this end point

    Secondary: Parts A and B: Unconfirmed Objective Response Rate (uORR)

    		 Close Top of page
    End point title
    		 Parts A and B: Unconfirmed Objective Response Rate (uORR)
    End point description
    uORR was calculated as the percentage of subjects with unconfirmed objective response per RECIST v1.1. Unconfirmed objective response is an unconfirmed best overall response of PR or CR. Objective response was derived as any PR or CR recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to <10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: percentage of subjects
        number (not applicable)
    0.0
    25.0
    0.0
    0.0
    0.0
    9.1
    No statistical analyses for this end point

    Secondary: Parts A and B: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Parts A and B: Disease Control Rate (DCR)
    End point description
    DCR was calculated as the percentage of subjects with disease control. Disease control was derived as any CR, PR, or stable disease reported during the study. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to <10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: percentage of subjects
        number (not applicable)
    66.7
    50.0
    25.0
    75.0
    37.5
    45.5
    No statistical analyses for this end point

    Secondary: Parts A and B: Median Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Parts A and B: Median Duration of Response (DOR)
    End point description
    DOR is defined as the time, in months, between date of the initial response (PR or CR) or date of first reduction of 50% in carbohydrate antigen 125 (CA-125), and date of the first documented disease progression or death due to any cause, whichever occurs first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to <10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Data is reported as Kaplan-Meier product-limit estimates. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. Number of subjects analysed indicates the censored subjects with at least a CR or PR. 9999= The median and the 95% confidence interval (CI) were not estimable due to insufficient number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    0 [6]
    2
    0 [7]
    0 [8]
    0 [9]
    1
    Units: months
        median (confidence interval 95%)
    ( to )
    9999 (9999 to 9999)
    ( to )
    ( to )
    ( to )
    9999 (9999 to 9999)
    Notes
    [6] - Only censored subjects with at least a CR or PR were analysed for this endpoint.
    [7] - Only censored subjects with at least a CR or PR were analysed for this endpoint.
    [8] - Only censored subjects with at least a CR or PR were analysed for this endpoint.
    [9] - Only censored subjects with at least a CR or PR were analysed for this endpoint.
    No statistical analyses for this end point

    Secondary: Parts A and B: Progression Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Parts A and B: Progression Free Survival (PFS)
    End point description
    PFS duration is defined as the time, in months, elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. 9999= The upper limit of 95% CI was not estimable due to low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until disease progression/recurrence or death from any cause, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: months
        median (confidence interval 95%)
    2.3 (1.7 to 9999)
    2.3 (0.3 to 9999)
    1.8 (1.0 to 3.2)
    1.9 (0.9 to 3.5)
    1.2 (0.8 to 4.2)
    1.8 (1.3 to 5.2)
    No statistical analyses for this end point

    Secondary: Parts A and B: PFS Rate at Months 6 and 12

    		 Close Top of page
    End point title
    		 Parts A and B: PFS Rate at Months 6 and 12
    End point description
    PFS is defined as duration elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. Data for PFS rate is reported as Kaplan-Meier product-limit estimates and include Brookmeyer-Crowley confidence intervals. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. 0.000 denotes that data was not available due to low number of subjects with events. n=number of subjects analysed at the given time point. 9999 denotes that data was not available due to all subjects discontinuing the study before the stipulated 12-month PFS duration i.e., no subjects were analysed at Month 12 in Part B.
    End point type
    Secondary
    End point timeframe
    Months 6 and 12
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: proportion of subjects
    number (confidence interval 95%)
        Month 6
    0.0 (0.000 to 0.000)
    0.2 (0.0 to 0.5)
    0.1 (0.0 to 0.4)
    0.0 (0.000 to 0.000)
    0.1 (0.0 to 0.4)
    0.2 (0.0 to 0.4)
        Month 12 (n=3, 8, 0, 0, 0, 0)
    0.0 (0.000 to 0.000)
    0.2 (0.0 to 0.5)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Parts A and B: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Parts A and B: Overall Survival (OS)
    End point description
    OS is defined as the time elapsed, in months, between treatment initiation and death from any cause. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. 9999= The upper limit of 95% CI was not estimable due to low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until death from any cause, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: months
        median (confidence interval 95%)
    13.8 (12.5 to 9999)
    9999 (1.9 to 9999)
    17.5 (3.8 to 9999)
    4.7 (0.9 to 13.4)
    5.2 (1.9 to 9999)
    11.7 (3.9 to 9999)
    No statistical analyses for this end point

    Secondary: Parts A and B: OS Rate at Months 12 and 18

    		 Close Top of page
    End point title
    		 Parts A and B: OS Rate at Months 12 and 18
    End point description
    OS is defined as the time elapsed, in months, between treatment initiation and death from any cause. Data for OS rate is reported as Kaplan-Meier product-limit estimates and includes Brookmeyer-Crowley confidence intervals. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. 9999= The median and 95% CI were not estimable due to low number of subjects with events. n=number of subjects analysed at the given time point.
    End point type
    Secondary
    End point timeframe
    Months 12 and 18
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    3
    8
    8
    8
    8
    11
    Units: proportion of subjects
    number (confidence interval 95%)
        Month 12
    1.0 (1.0 to 1.0)
    0.5 (0.2 to 0.8)
    0.9 (0.4 to 1.0)
    0.3 (0.0 to 0.6)
    0.4 (0.1 to 0.7)
    0.4 (0.1 to 0.7)
        Month 18 (n= 1, 1, 8, 8, 8, 11)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    0.5 (0.2 to 0.8)
    0.1 (0.0 to 0.4)
    0.4 (0.1 to 0.7)
    0.3 (0.0 to 0.6)
    No statistical analyses for this end point

    Secondary: Part A: Area Under the Curve From Time 0 to 4 Hours (AUC0-4H) of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part A: Area Under the Curve From Time 0 to 4 Hours (AUC0-4H) of Debio 1143 and Debio 1143-MET1 [10]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug in Part A. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 0.5, 1.5, 4 hours post-dose on Days 1 and 15, predose, 1.5, 4 hours post-dose on Days 8 and 22; Cycle 3: predose, 0.5, 1.5, 4 hours post-dose on Day 1 and predose, 1.5, 4 hours post-dose on Day 15 (each cycle=28 days)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    8
    Units: hours*nanograms per millilitre (h*ng/mL)
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 1
    6200.28 ( 330.246 )
    4907.15 ( 2496.914 )
        Debio 1143: Cycle 1 Day 8 (n=3, 7)
    4321.40 ( 1127.611 )
    5861.53 ( 3764.659 )
        Debio 1143: Cycle 1 Day 15 (n=3, 7)
    5081.21 ( 868.905 )
    5114.03 ( 3168.408 )
        Debio 1143: Cycle 1 Day 22 (n=3, 5)
    4517.00 ( 3539.938 )
    4086.09 ( 2516.921 )
        Debio 1143: Cycle 3 Day 1 (n=3, 5)
    4053.97 ( 3005.430 )
    6844.02 ( 4940.667 )
        Debio 1143: Cycle 3 Day 15 (n=2, 4)
    4725.37 ( 2033.252 )
    5934.72 ( 2251.520 )
        Debio 1143-MET1: Cycle 1 Day 1
    2624.48 ( 953.275 )
    1662.25 ( 957.856 )
        Debio 1143-MET1: Cycle 1 Day 8 (n=3, 7)
    3884.59 ( 565.589 )
    5133.24 ( 3794.465 )
        Debio 1143-MET1: Cycle 1 Day 15 (n=3, 7)
    2104.06 ( 325.456 )
    1673.48 ( 986.138 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=3, 5)
    3634.33 ( 1591.770 )
    5064.61 ( 4242.170 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=3, 5)
    983.62 ( 501.515 )
    2617.59 ( 2250.993 )
        Debio 1143-MET1: Cycle 3 Day 15 (n=2, 4)
    3255.14 ( 513.699 )
    2208.80 ( 775.572 )
    No statistical analyses for this end point

    Secondary: Part B: AUC0-4H of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part B: AUC0-4H of Debio 1143 and Debio 1143-MET1 [11]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug in Part B. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 1.5, 4 hours post-dose on Days 1 and 22; Cycle 3: predose, 1.5, 4 hours post-dose on Day 1 (each cycle = 28 days)
    Notes
    [11] - 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: This endpoint was applicable only for Part B arm groups of the study.
    End point values
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    7
    7
    8
    10
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 1
    6842.88 ( 3251.994 )
    5552.70 ( 4559.658 )
    5149.10 ( 1922.588 )
    7619.75 ( 3287.399 )
        Debio 1143: Cycle 1 Day 22 (n=7,6,5,8)
    7167.67 ( 4161.553 )
    5668.59 ( 3536.016 )
    3218.09 ( 1137.952 )
    6801.02 ( 1841.871 )
        Debio 1143: Cycle 3 Day 1 (n=2,2,3,7)
    5674.83 ( 757.917 )
    3248.39 ( 3165.907 )
    2117.23 ( 970.849 )
    5920.77 ( 2206.953 )
        Debio 1143-MET1: Cycle 1 Day 1 (n=7,5,8,10)
    2737.56 ( 1280.628 )
    3440.08 ( 2274.864 )
    2255.49 ( 1153.863 )
    3140.29 ( 1139.965 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=7,6,5,8)
    5938.44 ( 2187.477 )
    10100.42 ( 3889.091 )
    5404.44 ( 4032.522 )
    7085.47 ( 5196.199 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=2,2,3,7)
    3409.44 ( 2059.973 )
    1587.21 ( 1838.618 )
    2381.90 ( 2767.733 )
    2128.83 ( 1581.498 )
    No statistical analyses for this end point

    Secondary: Part A: Area Under the Curve From Time 0 to 8 Hours (AUC0-8H) of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part A: Area Under the Curve From Time 0 to 8 Hours (AUC0-8H) of Debio 1143 and Debio 1143-MET1 [12]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug in Part A. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 0.5, 1.5, 4, 8 hours post-dose on Days 1 and 15, and predose, 1.5, 4, 8 hours post-dose on Day 8; Cycle 3: predose, 0.5, 1.5, 4, 8 hours post-dose on Day 1 and predose, 1.5, 4, 8 hours post-dose on Day 15 (each cycle = 28 days)
    Notes
    [12] - 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: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    7
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 1
    8954.45 ( 1347.640 )
    8497.84 ( 3213.996 )
        Debio 1143: Cycle 1 Day 8
    6699.18 ( 1315.190 )
    9437.55 ( 6036.801 )
        Debio 1143: Cycle 1 Day 15
    7280.65 ( 945.078 )
    8024.00 ( 5036.125 )
        Debio 1143: Cycle 3 Day 1 (n=2, 4)
    4623.23 ( 2089.994 )
    10627.09 ( 6520.082 )
        Debio 1143: Cycle 3 Day 15 (n=2, 4)
    6864.95 ( 1815.779 )
    9072.05 ( 3529.268 )
        Debio 1143-MET1: Cycle 1 Day 1
    5940.42 ( 2217.500 )
    5128.38 ( 2307.490 )
        Debio 1143-MET1: Cycle 1 Day 8
    7743.38 ( 1258.029 )
    10646.90 ( 8177.450 )
        Debio 1143-MET1: Cycle 1 Day 15
    4921.26 ( 741.691 )
    4304.95 ( 2105.077 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=2, 4)
    2315.46 ( 1568.487 )
    6632.52 ( 6610.503 )
        Debio 1143-MET1: Cycle 3 Day 15 (n=2, 4)
    6011.84 ( 429.313 )
    6225.18 ( 2315.768 )
    No statistical analyses for this end point

    Secondary: Part A: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part A: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1 [13]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part A. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: Predose,0.5,1.5,4,8 hours post-dose (Days 1 and 15), predose,1.5,4,8 hours post-dose (Day 8), predose,1.5,4 hours post-dose (Day 22); Cycle 3: predose,0.5,1.5,4,8 hours post-dose (Day 1), predose,1.5,4,8 hours post-dose (Day 15) (Cycle=28 days)
    Notes
    [13] - 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: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    8
    Units: ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 1
    3063.33 ( 771.838 )
    2020.63 ( 1015.945 )
        Debio 1143: Cycle 1 Day 8 (n=3, 7)
    1656.67 ( 568.624 )
    2132.71 ( 1346.859 )
        Debio 1143: Cycle 1 Day 15 (n=3, 7)
    2426.67 ( 567.656 )
    1956.29 ( 1137.771 )
        Debio 1143: Cycle 1 Day 22 (n=3, 5)
    2037.00 ( 1637.415 )
    1528.96 ( 910.236 )
        Debio 1143: Cycle 3 Day 1 (n=3, 5)
    1954.00 ( 1119.459 )
    3071.00 ( 1928.848 )
        Debio 1143: Cycle 3 Day 15 (n=2, 4)
    1970.00 ( 1244.508 )
    2265.00 ( 886.397 )
        Debio 1143-MET1: Cycle 1 Day 1
    989.67 ( 344.515 )
    972.50 ( 489.140 )
        Debio 1143-MET1: Cycle 1 Day 8 (n=3, 7)
    1193.33 ( 222.336 )
    1733.23 ( 1184.636 )
        Debio 1143-MET1: Cycle 1 Day 15 (n=3, 7)
    868.00 ( 117.051 )
    915.86 ( 390.840 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=3, 5)
    1088.33 ( 581.758 )
    1658.68 ( 1339.093 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=3, 5)
    611.00 ( 376.227 )
    1343.60 ( 1078.400 )
        Debio 1143-MET1: Cycle 3 Day 15 (n=2, 4)
    1177.00 ( 272.943 )
    1148.50 ( 458.398 )
    No statistical analyses for this end point

    Secondary: Part B: Cmax of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part B: Cmax of Debio 1143 and Debio 1143-MET1 [14]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part B. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 1.5, 4 hours post-dose on Days 1 and 22; Cycle 3: predose, 1.5, 4 hours post-dose on Day 1 (each cycle = 28 days)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part B arm groups of the study.
    End point values
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    8
    8
    8
    11
    Units: ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 1
    2839.5 ( 1293.43 )
    2266.1 ( 1830.74 )
    2331.3 ( 823.28 )
    2850.0 ( 1413.87 )
        Debio 1143: Cycle 1 Day 22 (n=8, 6, 5, 10)
    2786.3 ( 1591.66 )
    2065.8 ( 1205.31 )
    1327.0 ( 416.30 )
    2891.0 ( 860.28 )
        Debio 1143: Cycle 3 Day 1 (n=3, 2, 3, 7)
    2183.3 ( 496.42 )
    1726.0 ( 1094.60 )
    975.3 ( 179.70 )
    2271.4 ( 954.80 )
        Debio 1143-MET1: Cycle 1 Day 1
    1077.38 ( 473.925 )
    1070.71 ( 808.979 )
    1190.00 ( 439.686 )
    1320.00 ( 483.919 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=8, 6, 5, 10)
    1888.50 ( 668.598 )
    2886.67 ( 915.394 )
    1782.80 ( 1074.434 )
    2289.10 ( 1414.128 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=3, 2, 3, 7)
    808.67 ( 748.505 )
    738.00 ( 724.077 )
    965.33 ( 982.152 )
    891.29 ( 488.887 )
    No statistical analyses for this end point

    Secondary: Part A: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part A: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 [15]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part A. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint. 0.000= Data is not available as zero subjects were analysed at the given timepoint. 9999= The standard deviation cannot be calculated for 1 subject.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose on Days 3, 8, 15, 17 and 22; Cycle 3: predose on Days 1, 3, 15, 17; Cycle 6: predose on Day 1 (each cycle = 28 days)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    8
    Units: ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 3
    113.10 ( 31.892 )
    169.50 ( 120.014 )
        Debio 1143: Cycle 1 Day 8
    118.27 ( 30.751 )
    173.35 ( 113.797 )
        Debio 1143: Cycle 1 Day 15 (n=1, 5)
    7.34 ( 9999 )
    5.22 ( 2.844 )
        Debio 1143: Cycle 1 Day 17
    99.37 ( 19.290 )
    133.57 ( 86.239 )
        Debio 1143: Cycle 1 Day 22 (n=3, 5)
    83.53 ( 19.630 )
    173.70 ( 135.079 )
        Debio 1143: Cycle 3 Day 1 (n=1, 2)
    10.20 ( 9999 )
    4.72 ( 0.410 )
        Debio 1143: Cycle 3 Day 3 (n=3, 2)
    110.47 ( 13.808 )
    97.20 ( 37.901 )
        Debio 1143: Cycle 3 Day 15 (n=0, 2)
    0.000 ( 0.000 )
    8.71 ( 6.640 )
        Debio 1143: Cycle 3 Day 17 (n=2, 3)
    118.00 ( 16.971 )
    136.37 ( 81.772 )
        Debio 1143: Cycle 6 Day 1 (n=0, 1)
    0.000 ( 0.000 )
    5.31 ( 9999 )
        Debio 1143-MET1: Cycle 1 Day 3
    453.33 ( 180.059 )
    620.10 ( 434.376 )
        Debio 1143-MET1: Cycle 1 Day 8
    387.00 ( 145.812 )
    793.65 ( 953.516 )
        Debio 1143-MET1: Cycle 1 Day 15 (n=1, 3)
    33.30 ( 9999 )
    6.39 ( 3.241 )
        Debio 1143-MET1: Cycle 1 Day 17
    543.00 ( 154.182 )
    531.93 ( 560.633 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=3, 5)
    367.33 ( 289.588 )
    805.78 ( 961.228 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=1, 2)
    6.97 ( 9999 )
    23.65 ( 27.655 )
        Debio 1143-MET1: Cycle 3 Day 3 (n=3, 2)
    443.67 ( 172.631 )
    1157.50 ( 1304.612 )
        Debio 1143-MET1: Cycle 3 Day 15 (n=0, 2)
    0.000 ( 0.000 )
    13.55 ( 9.687 )
        Debio 1143-MET1: Cycle 3 Day 17 (n=2, 3)
    611.00 ( 322.441 )
    639.67 ( 387.727 )
        Debio 1143-MET1: Cycle 6 Day 1 (n=0, 1)
    0.000 ( 0.000 )
    3.15 ( 9999 )
    No statistical analyses for this end point

    Secondary: Part B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1

    		 Close Top of page
    End point title
    		 Part B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 [16]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part B. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint. 0.000= Data is not available as zero subjects were analysed at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose on Days 8 and 22; Cycle 3: predose on Day 1 (each cycle = 28 days)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part B arm groups of the study.
    End point values
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    8
    8
    7
    10
    Units: ng/mL
    arithmetic mean (standard deviation)
        Debio 1143: Cycle 1 Day 8 (n=6, 7, 7, 10)
    198.05 ( 143.494 )
    167.20 ( 112.649 )
    192.86 ( 130.457 )
    143.39 ( 44.663 )
        Debio 1143: Cycle 1 Day 22 (n=8, 6, 5, 10)
    150.29 ( 80.118 )
    221.60 ( 140.039 )
    130.92 ( 50.555 )
    146.39 ( 50.852 )
        Debio 1143: Cycle 3 Day 1 (n=2, 2, 2, 5)
    3.24 ( 0.721 )
    11.08 ( 12.056 )
    3.50 ( 0.318 )
    4.94 ( 2.137 )
        Debio 1143-MET: Cycle 1 Day 8 (n=6, 8, 7, 10)
    693.33 ( 983.009 )
    1917.89 ( 1826.669 )
    1005.20 ( 1150.843 )
    1118.40 ( 710.330 )
        Debio 1143-MET1: Cycle 1 Day 22 (n=8, 6, 5, 10)
    658.50 ( 557.846 )
    2103.33 ( 1410.308 )
    830.20 ( 827.444 )
    1113.04 ( 811.962 )
        Debio 1143-MET1: Cycle 3 Day 1 (n=2, 2, 0, 3)
    2.84 ( 0.255 )
    14.35 ( 11.809 )
    0.000 ( 0.000 )
    10.30 ( 3.751 )
    No statistical analyses for this end point

    Secondary: Part A: Serum Trough Concentration of Nivolumab

    		 Close Top of page
    End point title
    		 Part A: Serum Trough Concentration of Nivolumab [17]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part A. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint. 9999= the standard deviation cannot be calculated for 1 subject. 0.000=Data is not available as zero subjects were analysed at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 1.5, 8 hours post-dose on Day 15; Cycle 3: predose, 0.5, 1.5, 8 hours post-dose on Day 1 and predose, 1.5 hours post-dose on Day 15 (each cycle = 28 days)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part A arm groups of the study.
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab
    Number of subjects analysed
    3
    7
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 15
    21366.67 ( 4808.673 )
    22271.43 ( 7553.744 )
        Cycle 3 Day 1 (n=1, 1)
    43500.00 ( 9999 )
    32700.00 ( 9999 )
        Cycle 3 Day 15 (n=0, 1)
    0.000 ( 0.000 )
    27100.00 ( 9999 )
    No statistical analyses for this end point

    Secondary: Part B: Serum Trough Concentration of Nivolumab

    		 Close Top of page
    End point title
    		 Part B: Serum Trough Concentration of Nivolumab [18]
    End point description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug of Part B. Number of subjects analysed indicates number of subjects available for analysis. Number analysed (n) indicates the number of subjects with available data for analysis at the given timepoint. 9999= the standard deviation cannot be calculated for 1 subject. 0.000= Data is not available as zero subjects were analysed at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1: predose, 1.5 hours post-dose on Day 15; Cycle 3: predose, 1.5 hours post-dose on Day 1 and Day 15; Cycle 6: predose on Day 1 (each cycle = 28 days)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was applicable only for Part B arm groups of the study.
    End point values
    		 Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    8
    7
    8
    10
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 15
    21312.5 ( 2942.51 )
    25414.3 ( 8766.68 )
    33725.0 ( 17751.28 )
    22332.0 ( 8864.61 )
        Cycle 3 Day 1 (n=1, 1, 0, 6)
    34100.0 ( 9999 )
    40600.0 ( 9999 )
    0.000 ( 0.000 )
    43866.7 ( 11670.08 )
        Cycle 3 Day 15 (n=0, 1, 0, 4)
    0.000 ( 0.000 )
    45400.0 ( 9999 )
    0.000 ( 0.000 )
    58400.0 ( 10492.22 )
        Cycle 6 Day 1 (n=0, 1, 0, 0)
    0.000 ( 0.000 )
    40400.0 ( 9999 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    No statistical analyses for this end point

    Secondary: Parts A and B: Time to Response (TTR)

    		 Close Top of page
    End point title
    		 Parts A and B: Time to Response (TTR)
    End point description
    The average of the time taken in days for PR is reported. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Safety analysis set included all enrolled subjects who received at least one dose of any study drug. Number of subjects analysed indicates number of subjects with at least a CR or PR.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    End point values
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab PartB:Cohort4(Gynaecologic Cancers):Debio1143 200 mg+Nivolumab
    Number of subjects analysed
    0 [19]
    2
    0 [20]
    0 [21]
    0 [22]
    1
    Units: days
        arithmetic mean (full range (min-max))
    ( to )
    82 (56 to 108)
    ( to )
    ( to )
    ( to )
    52 (52 to 52)
    Notes
    [19] - This endpoint was analysed only in subjects who had a response.
    [20] - This endpoint was analysed only in subjects who had a response.
    [21] - This endpoint was analysed only in subjects who had a response.
    [22] - This endpoint was analysed only in subjects who had a response.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From after the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy -1 day, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
    Adverse event reporting additional description
    Safety analysis set included all enrolled subjects who received at least one dose of any study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Part A: Debio 1143 150 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion over 30 minutes on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part A: Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab, 240mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab
    Reporting group description
    		 Subjects with gastrointestinal (GI) cancers received Debio 1143, 200mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Reporting group title
    Part B:Cohort4(Gynaecologic Cancers):Debio1143 200mg+Nivolumab
    Reporting group description
    		 Subjects with gynaecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

    Serious adverse events
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab Part B:Cohort4(Gynaecologic Cancers):Debio1143 200mg+Nivolumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    8 / 8 (100.00%)
    0 / 8 (0.00%)
    6 / 8 (75.00%)
    5 / 8 (62.50%)
    5 / 11 (45.45%)
         number of deaths (all causes)
    2
    4
    5
    7
    6
    7
         number of deaths resulting from adverse events
    0
    0
    0
    3
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Pancreatitis acute
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Biliary obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Hepatic failure
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Portal vein thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myositis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 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
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    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
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A: Debio 1143 150 mg + Nivolumab Part A: Debio 1143 200 mg + Nivolumab Part B: Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab Part B: Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab Part B: Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab Part B:Cohort4(Gynaecologic Cancers):Debio1143 200mg+Nivolumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    8 / 8 (100.00%)
    8 / 8 (100.00%)
    8 / 8 (100.00%)
    11 / 11 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Vascular disorders
    Lymphoedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    3
    1
    0
    0
    3
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Facial pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    6 / 8 (75.00%)
    3 / 8 (37.50%)
    2 / 8 (25.00%)
    2 / 11 (18.18%)
         occurrences all number
    1
    1
    6
    3
    2
    2
    Generalised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    3 / 11 (27.27%)
         occurrences all number
    0
    2
    1
    1
    0
    3
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Reproductive system and breast disorders
    Intermenstrual bleeding
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Pelvic pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vaginal fistula
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Catarrh
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    3
    1
    1
    1
    Pneumonitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Throat irritation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    5 / 11 (45.45%)
         occurrences all number
    0
    1
    2
    2
    1
    5
    Amylase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    1
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    4 / 11 (36.36%)
         occurrences all number
    0
    1
    3
    2
    1
    4
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Lipase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    2
    2
    1
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    1
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood corticotrophin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood creatine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Cortisol decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Craniocerebral injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    VIth nerve injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nervous system disorders
    Bell's palsy
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Memory impairment
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Neuralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Vocal cord paralysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    1 / 8 (12.50%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    4 / 11 (36.36%)
         occurrences all number
    0
    5
    2
    2
    2
    4
    Hyperleukocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Lymph node pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    3 / 11 (27.27%)
         occurrences all number
    0
    2
    2
    1
    1
    4
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    3 / 8 (37.50%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    3 / 11 (27.27%)
         occurrences all number
    0
    2
    4
    1
    0
    3
    Dry mouth
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    Dysphagia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Gingival pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    3 / 8 (37.50%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    2
    2
    3
    2
    Oral pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Stomatitis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    3
    1
    2
    1
    0
    Hepatobiliary disorders
    Hepatic cytolysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Leukoplakia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 8 (37.50%)
    4 / 8 (50.00%)
    2 / 8 (25.00%)
    2 / 8 (25.00%)
    3 / 11 (27.27%)
         occurrences all number
    0
    4
    4
    2
    3
    3
    Rash maculo-papular
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    3 / 8 (37.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    1
    0
    3
    0
    1
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pemphigoid
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rash macular
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    2
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Skin reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Renal failure
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    Urinary incontinence
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Urinary retention
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    2
    0
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    0
    1
    3
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sacral pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Ear infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Fungal foot infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lip infection
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Mucosal infection
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 8 (25.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    0 / 11 (0.00%)
         occurrences all number
    1
    2
    0
    1
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Listeria encephalitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oral fungal infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pseudomonas infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Soft tissue infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    3 / 8 (37.50%)
    3 / 8 (37.50%)
    1 / 8 (12.50%)
    1 / 11 (9.09%)
         occurrences all number
    0
    2
    3
    3
    1
    1
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    0
    1
    0
    4
    Hypomagnesaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    1 / 8 (12.50%)
    3 / 11 (27.27%)
         occurrences all number
    0
    0
    1
    1
    1
    3
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 8 (12.50%)
    0 / 8 (0.00%)
    0 / 8 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jan 2019
    • Added that the subjects should have had no established standard therapeutic alternatives to the cancer treatment. • Advised that subjects with active ongoing infection requiring systemic antibiotic therapy, including active tuberculosis, were not eligible for enrolment. • Changed the duration of safety follow-up, TEAE monitoring, and SAE reporting period for withdrawn subjects to 5 months (previously, 90 days) after the last nivolumab infusion. • Expanded the list of prohibited medications.
    07 Nov 2019
    • Allowed the inclusion of subjects with haemoglobin levels of ≥9.0 grams/decilitre (g/dL). • Adjusted the subject population for Cohort 1 to allow the inclusion of subjects with extrapulmonary small-cell carcinomas or large cell neuroendocrine lung carcinoma. • Clarified that nasopharyngeal carcinoma was not allowed in Cohort 2. • Shortened the time window of thoracic or head and neck radiation >30 Gray (Gy) from within 3 months to 6 weeks prior to the start of treatment. • Allowed inclusion of subjects with vitiligo >Grade 1 as an ongoing toxicity of prior antineoplastic therapies. • Shortened the time window for blood transfusion from up to 4 weeks to 2 weeks prior to the start of treatment.
    03 Apr 2020
    • Added the clarification of the study treatment duration and the conditions under which treatment duration could be prolonged by 1 year for subjects who exceptionally continued study treatment beyond 13 cycles. • Added the clarification of the schedule of assessments for subjects who exceptionally continued study treatment beyond 13 cycles. • Added the clarification that the final analysis would be conducted 18 months after the last subject was included in the study (LPI) or 60 days from last subject last visit (LPLV), whichever occurs first. • Updated the inclusion criteria to align the washout period of previous investigational monoclonal antibodies (mAbs) to 4 weeks or at least the duration of 1 treatment cycle whichever is the longest to prevent a potential carry-over effect. • Updated language for prohibited concomitant medication for strong P-glycoprotein (P-gp) inhibitors/inducers and cytochrome P450 (CYP) 3A substrates. CYP 2B6 and 1A2 substrates were added as drugs to be used with caution and closely monitored based on new data. In addition, drugs with a known risk of QTc prolongation were added as medications to be used with caution. Furthermore, language on possible drug-drug interaction (DDI) concerning hormonal contraception was corrected.

    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-Mon May 06 09:24:48 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA