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    Clinical Trial Results:
    A Phase 2 Study of INCMGA00012 in Participants With Metastatic Merkel Cell Carcinoma

    Summary
    EudraCT number
    		 2018-001627-39
    Trial protocol
    		 CZ   DE   FR   ES   GB   PL   HU   IT  
    Global end of trial date
    27 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jun 2025
    First version publication date
    26 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    INCMGA 0012-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Incyte Corporation
    Sponsor organisation address
    1801 Augustine Cutoff, Wilmington, United States, 19803
    Public contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Scientific contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.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
    27 Jun 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study was conducted to determine the efficacy of retifanlimab in terms of the objective response rate in chemotherapy-naive participants with metastatic Merkel Cell carcinoma (MCC).
    Protection of trial subjects
    This study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and was conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations in which the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Feb 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    France: 22
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    Italy: 40
    Country: Number of subjects enrolled
    Poland: 9
    Country: Number of subjects enrolled
    United States: 16
    Worldwide total number of subjects
    107
    EEA total number of subjects
    80
    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)
    35
    From 65 to 84 years
    63
    85 years and over
    9

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were enrolled and treated at 34 study centers in Italy, France, the United States, Poland, Canada, Switzerland, Hungary, the Czech Republic, Germany, Spain, and the United Kingdom.

    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
    		 Chemotherapy: Naïve
    Arm description
    		 Participants with recurrent, advanced locoregional disease or distant metastatic disease who did not receive any prior chemotherapy received retifanlimab 500 milligrams (mg), administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 28-day cycle (Q4W).
    Arm type
    		 Experimental

    Investigational medicinal product name
    retifanlimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    unit dose strength/dosage level = 500 mg Q4W; administered over 60 minutes (+ 15 minutes)

    Arm title
    		 Chemotherapy: Refractory
    Arm description
    		 Participants with disease not responding to prior chemotherapy received retifanlimab 500 mg, administered by IV infusion over 60 minutes on Day 1 Q4W.
    Arm type
    		 Experimental

    Investigational medicinal product name
    retifanlimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    unit dose strength/dosage level = 500 mg Q4W; administered over 60 minutes (+ 15 minutes)

    Number of subjects in period 1
    		Chemotherapy: Naïve Chemotherapy: Refractory
    Started
    101
    6
    Safety Evaluable Population
    101
    6
    Enrolled Population
    101
    6
    Full Analysis Set
    65
    6
    Completed
    0
    0
    Not completed
    101
    6
         Consent withdrawn by subject
    17
    -
         Death
    38
    3
         Lost to follow-up
    4
    -
         Discontinued Due to End of Study
    42
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Chemotherapy: Naïve
    Reporting group description
    		 Participants with recurrent, advanced locoregional disease or distant metastatic disease who did not receive any prior chemotherapy received retifanlimab 500 milligrams (mg), administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 28-day cycle (Q4W).

    Reporting group title
    Chemotherapy: Refractory
    Reporting group description
    		 Participants with disease not responding to prior chemotherapy received retifanlimab 500 mg, administered by IV infusion over 60 minutes on Day 1 Q4W.

    Reporting group values
    		 Chemotherapy: Naïve Chemotherapy: Refractory Total
    Number of subjects
    		 101 6 107
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 32 3 35
        From 65-84 years
    		 60 3 63
        85 years and over
    		 9 0 9
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 71.1 ( 10.44 ) 63.8 ( 10.46 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 33 1 34
        Male
    		 68 5 73
    Race
    Units: Subjects
        Asian
    		 1 0 1
        White
    		 78 6 84
        Unknown or Not Reported
    		 22 0 22
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 0 1
        Not Hispanic or Latino
    		 75 6 81
        Unknown or Not Reported
    		 25 0 25

    End points

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    End points reporting groups
    Reporting group title
    Chemotherapy: Naïve
    Reporting group description
    		 Participants with recurrent, advanced locoregional disease or distant metastatic disease who did not receive any prior chemotherapy received retifanlimab 500 milligrams (mg), administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 28-day cycle (Q4W).

    Reporting group title
    Chemotherapy: Refractory
    Reporting group description
    		 Participants with disease not responding to prior chemotherapy received retifanlimab 500 mg, administered by IV infusion over 60 minutes on Day 1 Q4W.

    Subject analysis set title
    All Participants: PK Population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants with recurrent, advanced locoregional disease or distant metastatic disease who did not receive any prior chemotherapy received retifanlimab 500 mg, administered by IV infusion over 60 minutes on Day 1 Q4W.

    Primary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    ORR=percentage of participants with a confirmed overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by Independent Central Radiographic Review (ICR), at any post-Baseline visit until the first progressive disease (PD) or new anti-cancer therapy. CR: disappearance of all target/non-target lesions and no appearance of new lesions. Any pathological lymph nodes (target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or ≥30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Full Analysis Set (FAS): all enrolled participants who received ≥1 dose of study drug as of 15 October 2020 (selected to allow for ≥60 chemotherapy-naïve participants to be followed for at least 6 months after first response assessment).
    End point type
    Primary
    End point timeframe
    up to 26.8 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    65 [2]
    0 [3]
    Units: percentage of participants
        number (confidence interval 95%)
    52.3 (39.5 to 64.9)
    ( to )
    Notes
    [2] - FAS. Analysis was based on the chemotherapy-naïve subset of the FAS.
    [3] - FAS. Analysis was based on the chemotherapy-naïve subset of the FAS.
    No statistical analyses for this end point

    Secondary: Duration of response (DOR)

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    End point title
    		 Duration of response (DOR)
    End point description
    DOR=time from an initial objective response (CR or PR) per RECIST v1.1 until PD, or death due to any cause, as determined by ICR. CR: disappearance of all target/non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or a ≥30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. A Kaplan-Meier estimate (estimated median) of the distribution function is reported. Safety Evaluable Population (SAP): all enrolled participants who received ≥1 dose of study drug. Analysis was based on the chemotherapy-naïve subset of the population. 9999=The median and the upper limit of the confidence interval were not estimable because too few participants had disease progression or died.
    End point type
    Secondary
    End point timeframe
    up to 55.3 months
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    55 [4]
    0 [5]
    Units: months
        number (confidence interval 95%)
    9999 (22.87 to 9999)
    ( to )
    Notes
    [4] - SAP. Participants with confirmed CR/PR prior to PD or start of new anticancer therapy were assessed.
    [5] - SAP. Participants with confirmed CR/PR prior to PD or start of new anticancer therapy were assessed.
    No statistical analyses for this end point

    Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

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    End point title
    		 Number of participants with any treatment-emergent adverse event (TEAE)
    End point description
    An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as either an AE reported for the first time or a worsening of a pre-existing event after the first dose of study drug until 90 days after the last dose of study drug. An AE with onset on/after starting a new anticancer therapy was not summarized as a TEAE.
    End point type
    Secondary
    End point timeframe
    up to 846 days (up to approximately 2.3 years)
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    101 [6]
    6 [7]
    Units: participants
        number (not applicable)
    92
    5
    Notes
    [6] - Safety Evaluable Population
    [7] - Safety Evaluable Population
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause. Analysis was based on the chemotherapy-naïve subset of the population. Median overall survival time was estimated using the Kaplan-Meier method. CI for median overall survival time was calculated using the method of Brookmeyer and Crowley. 9999=The median and the upper limit of the confidence interval were not estimable because too few participants died.
    End point type
    Secondary
    End point timeframe
    up to 60.4 months
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    101 [8]
    0 [9]
    Units: months
        median (confidence interval 95%)
    9999 (45.24 to 9999)
    ( to )
    Notes
    [8] - Safety Evaluable Population
    [9] - Safety Evaluable Population
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

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    End point title
    		 Disease Control Rate (DCR)
    End point description
    DCR was defined as the percentage of participants with a confirmed overall response (CR and PR) or stable disease (SD) (non-CR/non-PD) lasting at least 6 months from the start of treatment, until the first PD or new anti-cancer therapy, per RECIST v1.1 as determined by ICR. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. Analysis was based on the chemotherapy-naïve subset of the population. CIs were calculated based on the exact method for binomial distributions.
    End point type
    Secondary
    End point timeframe
    up to 57.1 months
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    101 [10]
    0 [11]
    Units: percentage of participants
        number (confidence interval 95%)
    60.4 (50.2 to 70.0)
    ( to )
    Notes
    [10] - Safety Evaluable Population
    [11] - Safety Evaluable Population
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS)

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    End point title
    		 Progression-free Survival (PFS)
    End point description
    According to RESIST v1.1, PFS was defined the time from the start of therapy until disease progression, or death due to any cause, as determined by ICR. Evaluation of target lesions: PD: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered PD). Evaluation of non-target lesions: PD: Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered PD). Analysis was based on the chemotherapy-naïve subset of the population. Median PFS time was estimated using the Kaplan-Meier method. The CI for median PFS time was calculated using the method of Brookmeyer and Crowley.
    End point type
    Secondary
    End point timeframe
    up to 57.1 months
    End point values
    		 Chemotherapy: Naïve Chemotherapy: Refractory
    Number of subjects analysed
    101 [12]
    0 [13]
    Units: months
        median (confidence interval 95%)
    16.03 (9.03 to 32.23)
    ( to )
    Notes
    [12] - Safety Evaluable Population
    [13] - Safety Evaluable Population
    No statistical analyses for this end point

    Secondary: First-dose Cmax of retifanlimab

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    End point title
    		 First-dose Cmax of retifanlimab
    End point description
    Cmax was defined as the maximum observed plasma concentration. The Pharmacokinetic (PK) Evaluable Population was comprised of all participants who received at least 1 dose of study drug and have provided a Baseline and at least 1 post-dose PK sample.
    End point type
    Secondary
    End point timeframe
    preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1
    End point values
    		 All Participants: PK Population
    Number of subjects analysed
    102 [14]
    Units: micrograms per milliliter (μg/mL)
        arithmetic mean (standard deviation)
    144 ( 32.6 )
    Notes
    [14] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: First-dose Cmin of retifanlimab

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    End point title
    		 First-dose Cmin of retifanlimab
    End point description
    Cmin was defined as the minimum observed plasma concentration over the dose interval.
    End point type
    Secondary
    End point timeframe
    preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1
    End point values
    		 All Participants: PK Population
    Number of subjects analysed
    102 [15]
    Units: μg/mL
        arithmetic mean (standard deviation)
    20.5 ( 7.23 )
    Notes
    [15] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: First-dose AUC0-t of retifanlimab

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    End point title
    		 First-dose AUC0-t of retifanlimab
    End point description
    AUC0-t was defined as the area under the plasma concentration-time curve from time zero to time t.
    End point type
    Secondary
    End point timeframe
    preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1
    End point values
    		 All Participants: PK Population
    Number of subjects analysed
    102 [16]
    Units: day*mg/L
        arithmetic mean (standard deviation)
    1770 ( 549 )
    Notes
    [16] - PK Evaluable Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    up to 846 days (up to approximately 2.3 years)
    Adverse event reporting additional description
    TEAEs (AEs reported for the first time/worsening of pre-existing events after the first dose of study drug until 90 days after the last dose of study drug) are reported for the Safety Evaluable Population (enrolled participants who received ≥1 dose of study drug). AEs with onset on/after starting new anticancer therapy were not summarized as TEAEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Chemotherapy: Naïve
    Reporting group description
    		 Participants with recurrent, advanced locoregional disease or distant metastatic disease who did not receive any prior chemotherapy received retifanlimab 500 milligrams (mg), administered by intravenous (IV) infusion over 60 minutes on Day 1 of each 28-day cycle (Q4W).

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    Chemotherapy: Refractory
    Reporting group description
    		 Participants with disease not responding to prior chemotherapy received retifanlimab 500 mg, administered by IV infusion over 60 minutes on Day 1 Q4W.

    Serious adverse events
    		 Chemotherapy: Naïve Total Chemotherapy: Refractory
    Total subjects affected by serious adverse events
         subjects affected / exposed
    26 / 101 (25.74%)
    28 / 107 (26.17%)
    2 / 6 (33.33%)
         number of deaths (all causes)
    39
    42
    3
         number of deaths resulting from adverse events
    4
    4
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ductal adenocarcinoma of pancreas
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 101 (2.97%)
    3 / 107 (2.80%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Concomitant disease progression
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 101 (1.98%)
    2 / 107 (1.87%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 101 (1.98%)
    2 / 107 (1.87%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Demyelinating polyneuropathy
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    2 / 101 (1.98%)
    2 / 107 (1.87%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eosinophilic fasciitis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    4 / 101 (3.96%)
    4 / 107 (3.74%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 101 (1.98%)
    2 / 107 (1.87%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 107 (0.93%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Chemotherapy: Naïve Total Chemotherapy: Refractory
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    83 / 101 (82.18%)
    88 / 107 (82.24%)
    5 / 6 (83.33%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    7 / 101 (6.93%)
    8 / 107 (7.48%)
    1 / 6 (16.67%)
         occurrences all number
    7
    8
    1
    Hypotension
         subjects affected / exposed
    2 / 101 (1.98%)
    3 / 107 (2.80%)
    1 / 6 (16.67%)
         occurrences all number
    2
    3
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    19 / 101 (18.81%)
    21 / 107 (19.63%)
    2 / 6 (33.33%)
         occurrences all number
    24
    27
    3
    Fatigue
         subjects affected / exposed
    10 / 101 (9.90%)
    13 / 107 (12.15%)
    3 / 6 (50.00%)
         occurrences all number
    12
    15
    3
    Oedema peripheral
         subjects affected / exposed
    7 / 101 (6.93%)
    7 / 107 (6.54%)
    0 / 6 (0.00%)
         occurrences all number
    7
    7
    0
    Pyrexia
         subjects affected / exposed
    11 / 101 (10.89%)
    13 / 107 (12.15%)
    2 / 6 (33.33%)
         occurrences all number
    14
    19
    5
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 101 (9.90%)
    10 / 107 (9.35%)
    0 / 6 (0.00%)
         occurrences all number
    11
    11
    0
    Nasal congestion
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    1
    Nasal turbinate hypertrophy
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Pleural effusion
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 107 (5.61%)
    0 / 6 (0.00%)
         occurrences all number
    6
    6
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 101 (5.94%)
    7 / 107 (6.54%)
    1 / 6 (16.67%)
         occurrences all number
    6
    7
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 101 (7.92%)
    8 / 107 (7.48%)
    0 / 6 (0.00%)
         occurrences all number
    8
    8
    0
    Amylase increased
         subjects affected / exposed
    8 / 101 (7.92%)
    8 / 107 (7.48%)
    0 / 6 (0.00%)
         occurrences all number
    11
    11
    0
    Blood creatinine increased
         subjects affected / exposed
    7 / 101 (6.93%)
    8 / 107 (7.48%)
    1 / 6 (16.67%)
         occurrences all number
    7
    8
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 101 (1.98%)
    3 / 107 (2.80%)
    1 / 6 (16.67%)
         occurrences all number
    2
    3
    1
    Lipase increased
         subjects affected / exposed
    9 / 101 (8.91%)
    9 / 107 (8.41%)
    0 / 6 (0.00%)
         occurrences all number
    11
    11
    0
    Low density lipoprotein increased
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 101 (0.00%)
    2 / 107 (1.87%)
    2 / 6 (33.33%)
         occurrences all number
    0
    2
    2
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    2 / 101 (1.98%)
    3 / 107 (2.80%)
    1 / 6 (16.67%)
         occurrences all number
    2
    3
    1
    Tremor
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 101 (5.94%)
    7 / 107 (6.54%)
    1 / 6 (16.67%)
         occurrences all number
    6
    7
    1
    Eye disorders
    Glaucoma
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    12 / 101 (11.88%)
    12 / 107 (11.21%)
    0 / 6 (0.00%)
         occurrences all number
    13
    13
    0
    Dyspepsia
         subjects affected / exposed
    4 / 101 (3.96%)
    5 / 107 (4.67%)
    1 / 6 (16.67%)
         occurrences all number
    6
    7
    1
    Dry mouth
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 107 (5.61%)
    0 / 6 (0.00%)
         occurrences all number
    6
    6
    0
    Diarrhoea
         subjects affected / exposed
    19 / 101 (18.81%)
    20 / 107 (18.69%)
    1 / 6 (16.67%)
         occurrences all number
    33
    34
    1
    Nausea
         subjects affected / exposed
    10 / 101 (9.90%)
    13 / 107 (12.15%)
    3 / 6 (50.00%)
         occurrences all number
    11
    14
    3
    Toothache
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Stomatitis
         subjects affected / exposed
    4 / 101 (3.96%)
    5 / 107 (4.67%)
    1 / 6 (16.67%)
         occurrences all number
    4
    5
    1
    Vomiting
         subjects affected / exposed
    5 / 101 (4.95%)
    6 / 107 (5.61%)
    1 / 6 (16.67%)
         occurrences all number
    5
    6
    1
    Skin and subcutaneous tissue disorders
    Hyperkeratosis
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    1
    Erythema
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 107 (5.61%)
    0 / 6 (0.00%)
         occurrences all number
    6
    6
    0
    Rash
         subjects affected / exposed
    7 / 101 (6.93%)
    7 / 107 (6.54%)
    0 / 6 (0.00%)
         occurrences all number
    8
    8
    0
    Pruritus
         subjects affected / exposed
    22 / 101 (21.78%)
    23 / 107 (21.50%)
    1 / 6 (16.67%)
         occurrences all number
    26
    27
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    8 / 101 (7.92%)
    10 / 107 (9.35%)
    2 / 6 (33.33%)
         occurrences all number
    8
    10
    2
    Hypophysitis
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    1
    Hyperthyroidism
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 107 (5.61%)
    0 / 6 (0.00%)
         occurrences all number
    6
    6
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    17 / 101 (16.83%)
    19 / 107 (17.76%)
    2 / 6 (33.33%)
         occurrences all number
    23
    28
    5
    Back pain
         subjects affected / exposed
    5 / 101 (4.95%)
    7 / 107 (6.54%)
    2 / 6 (33.33%)
         occurrences all number
    5
    7
    2
    Groin pain
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Muscle spasms
         subjects affected / exposed
    2 / 101 (1.98%)
    3 / 107 (2.80%)
    1 / 6 (16.67%)
         occurrences all number
    2
    3
    1
    Myalgia
         subjects affected / exposed
    5 / 101 (4.95%)
    7 / 107 (6.54%)
    2 / 6 (33.33%)
         occurrences all number
    5
    8
    3
    Pain in extremity
         subjects affected / exposed
    4 / 101 (3.96%)
    5 / 107 (4.67%)
    1 / 6 (16.67%)
         occurrences all number
    4
    5
    1
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    5 / 101 (4.95%)
    6 / 107 (5.61%)
    1 / 6 (16.67%)
         occurrences all number
    5
    6
    1
    COVID-19
         subjects affected / exposed
    10 / 101 (9.90%)
    10 / 107 (9.35%)
    0 / 6 (0.00%)
         occurrences all number
    11
    11
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 107 (0.93%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    Urinary tract infection
         subjects affected / exposed
    5 / 101 (4.95%)
    6 / 107 (5.61%)
    1 / 6 (16.67%)
         occurrences all number
    9
    10
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 101 (5.94%)
    6 / 107 (5.61%)
    0 / 6 (0.00%)
         occurrences all number
    6
    6
    0
    Dehydration
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 107 (1.87%)
    1 / 6 (16.67%)
         occurrences all number
    6
    7
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2018
    The primary purpose of this amendment was to address comments received from the United States Food and Drug Administration.
    04 Oct 2018
    The primary purpose of this amendment was to address comments received from the European Competent Authorities during the Voluntary Harmonization Procedure.
    05 Dec 2018
    The primary purpose of this amendment was to address comments received from Health Canada. Additional clarifications and administrative changes were also made.
    16 Aug 2019
    The primary purpose of this amendment was to expand the eligibility criteria to include participants with recurrent locoregional advanced disease in addition to participants with distant metastatic Merkel cell carcinoma.
    09 Apr 2020
    The primary purpose of this amendment was to clarify the definition of target lesions for participants who had progression in areas previously treated with locoregional therapy.
    22 Oct 2020
    The primary purpose of this amendment was to increase the sample size of the study to allow for more robust characterization of the primary and secondary endpoints.
    16 Dec 2021
    The primary purpose of this amendment was to update immune-related adverse event management guidelines to reflect updated published guidance and to provide guidance on the management of participants during the COVID-19 pandemic.
    18 May 2023
    The primary purpose of this amendment was to update the definition of the end of the study.

    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
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