Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02563002
Collaborator
(none)
307
2
86.7

Study Details

Study Description

Brief Summary

In this study, participants with stage IV Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) colorectal carcinoma (CRC) will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study hypothesis is that pembrolizumab will prolong progression-free survival (PFS) or overall survival (OS) compared to current SOC chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
307 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)
Actual Study Start Date :
Nov 30, 2015
Actual Primary Completion Date :
Feb 19, 2021
Anticipated Study Completion Date :
Feb 20, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Participants that have stopped the initial course of pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional).

Biological: pembrolizumab
MK-3475 SCH 900475 KEYTRUDA®
Other Names:
  • IV infusion
  • Active Comparator: Standard of Care (SOC)

    Participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Participants that have stopped pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional).

    Drug: mFOLFOX6
    Regimen consists of oxaliplatin 85 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle

    Drug: FOLFIRI
    Regimen consists of irinotecan 180 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-FU 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle

    Biological: pembrolizumab
    MK-3475 SCH 900475 KEYTRUDA®
    Other Names:
  • IV infusion
  • Biological: bevacizumab
    Other Names:
  • IV infusion
  • Biological: cetuximab
    Other Names:
  • IV infusion
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) Per RECIST1.1 As Assessed by Central Imaging Vendor [Up to approximately 59 months]

      PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Hazards ratio (HR) and associated 95% confidence intervals (CIs) from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.

    2. Overall Survival (OS) [Up to approximately 59 months]

      OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. HR and associated 95% CIs from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) Per RECIST1.1 as Assessed by Central Imaging Vendor [Up to approximately 59 months]

      ORR was defined as the percentage of the participants who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 as assessed by the central imaging vendor. The percentage of participants who experienced a CR or PR was presented for the first course of study treatment per protocol.

    2. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 59 months]

      An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course study treatment per protocol.

    3. Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 59 months]

      An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented for the first course study treatment per protocol.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start

    • Life expectancy of at least 3 months

    • Measurable disease

    • Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of standard of care (SOC) therapy or 120 days after the last pembrolizumab dose

    • Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose

    • Adequate organ function

    Exclusion Criteria:
    • Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study

    • Currently participating and receiving treatment in another study, or participated in a study of an investigational agent and received treatment, or used an investigational device within 4 weeks of randomization

    • Active autoimmune disease that has required systemic treatment in past 2 years

    • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization on this study

    • Radiation therapy within 4 weeks prior to randomization on this study and not recovered to baseline from adverse events due to radiation therapy

    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization on this study

    • Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)

    • Another malignancy that is progressing or requires active treatment with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma

    • Received a live vaccine within 30 days of planned start of study medication

    • Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C

    • Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis

    • Known history of active tuberculosis (Bacillus tuberculosis [TB])

    • Active infection requiring systemic therapy

    • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study

    • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of SOC or 120 days after the last dose of pembrolizumab

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02563002
    Other Study ID Numbers:
    • 3475-177
    • 2015-002024-89
    • 163238
    • MK-3475-177
    • KEYNOTE-177
    First Posted:
    Sep 29, 2015
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme LLC
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Of the 307 participants randomized in the study, 296 participants received study medication and were evaluable for safety analyses.
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Period Title: Overall Study
    STARTED 153 154
    Treated 153 143
    Received Second Course of Pembrolizumab 8 4
    Switched Over to Pembrolizumab 0 56
    COMPLETED 0 0
    NOT COMPLETED 153 154

    Baseline Characteristics

    Arm/Group Title Pembrolizumab Standard of Care (SOC) Total
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Total of all reporting groups
    Overall Participants 153 154 307
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    61.9
    (14.9)
    60.6
    (14.8)
    61.2
    (14.8)
    Sex: Female, Male (Count of Participants)
    Female
    82
    53.6%
    72
    46.8%
    154
    50.2%
    Male
    71
    46.4%
    82
    53.2%
    153
    49.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    11
    7.2%
    10
    6.5%
    21
    6.8%
    Not Hispanic or Latino
    128
    83.7%
    131
    85.1%
    259
    84.4%
    Unknown or Not Reported
    14
    9.2%
    13
    8.4%
    27
    8.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    24
    15.7%
    26
    16.9%
    50
    16.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    9
    5.9%
    5
    3.2%
    14
    4.6%
    White
    113
    73.9%
    116
    75.3%
    229
    74.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    7
    4.6%
    7
    4.5%
    14
    4.6%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS) Per RECIST1.1 As Assessed by Central Imaging Vendor
    Description PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Hazards ratio (HR) and associated 95% confidence intervals (CIs) from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
    Time Frame Up to approximately 59 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Measure Participants 153 154
    Median (95% Confidence Interval) [Months]
    16.5
    8.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Standard of Care (SOC)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments
    Method Log Rank
    Comments One-sided p-value based on log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.59
    Confidence Interval (2-Sided) 95%
    0.45 to 0.79
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on Cox regression model with Efron's method of tie handling with treatment as a covariate.
    2. Primary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. HR and associated 95% CIs from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
    Time Frame Up to approximately 59 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Measure Participants 153 154
    Median (95% Confidence Interval) [Months]
    NA
    36.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Standard of Care (SOC)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0359
    Comments
    Method Log Rank
    Comments One-sided p-value based on log rank test
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.53 to 1.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on Cox regression model with Efron's method of tie handling with treatment as a covariate.
    3. Secondary Outcome
    Title Overall Response Rate (ORR) Per RECIST1.1 as Assessed by Central Imaging Vendor
    Description ORR was defined as the percentage of the participants who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 as assessed by the central imaging vendor. The percentage of participants who experienced a CR or PR was presented for the first course of study treatment per protocol.
    Time Frame Up to approximately 59 months

    Outcome Measure Data

    Analysis Population Description
    All randomized participants
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Measure Participants 153 154
    Number (95% Confidence Interval) [Percentage of Participants]
    45.1
    29.5%
    33.1
    21.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab, Standard of Care (SOC)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0159
    Comments One-sided p-value based on Miettinen & Nurminen method.
    Method Miettinen & Nurminen method
    Comments
    Method of Estimation Estimation Parameter Difference in percentage
    Estimated Value 12.0
    Confidence Interval (2-Sided) 95%
    1.0 to 22.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on Miettinen & Nurminen method.
    4. Secondary Outcome
    Title Number of Participants Who Experienced an Adverse Event (AE)
    Description An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course study treatment per protocol.
    Time Frame Up to approximately 59 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Measure Participants 153 143
    Count of Participants [Participants]
    149
    97.4%
    142
    92.2%
    5. Secondary Outcome
    Title Number of Participants Who Discontinued Study Treatment Due to an AE
    Description An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented for the first course study treatment per protocol.
    Time Frame Up to approximately 59 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment
    Arm/Group Title Pembrolizumab Standard of Care (SOC)
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    Measure Participants 153 143
    Count of Participants [Participants]
    21
    13.7%
    20
    13%

    Adverse Events

    Time Frame Up to approximately 59 months
    Adverse Event Reporting Description All-cause mortality (ACM)=all randomized participants. AEs=all participants who received ≥1 dose of study treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression (NP), malignant NP, and disease progression not related to treatment are excluded. Per protocol, collection of AEs and ACM were planned to be done in first and second courses.
    Arm/Group Title Pembrolizumab First Course Standard of Care (SOC) First Course SOC Switched Over to Pembrolizumab Pembrolizumab-Second Course SOC Switched Over to Pembrolizumab-Second Course
    Arm/Group Description Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Eligible participants with documented disease progression following chemotherapy in SOC arm switched over to receive pembrolizumab for up to 35 cycles (approximately 2 years). Participants who received pembrolizumab as a first course and stopped the first course of pembrolizumab due to complete response (CR) or completed the first course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). Participants who switched over from SOC and received pembrolizumab and subsequently stopped the first course of pembrolizumab due to complete response (CR) or completed the first course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).
    All Cause Mortality
    Pembrolizumab First Course Standard of Care (SOC) First Course SOC Switched Over to Pembrolizumab Pembrolizumab-Second Course SOC Switched Over to Pembrolizumab-Second Course
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/153 (40.5%) 54/154 (35.1%) 24/56 (42.9%) 0/8 (0%) 0/4 (0%)
    Serious Adverse Events
    Pembrolizumab First Course Standard of Care (SOC) First Course SOC Switched Over to Pembrolizumab Pembrolizumab-Second Course SOC Switched Over to Pembrolizumab-Second Course
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/153 (40.5%) 75/143 (52.4%) 27/56 (48.2%) 2/8 (25%) 1/4 (25%)
    Blood and lymphatic system disorders
    Anaemia 1/153 (0.7%) 1 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Febrile neutropenia 1/153 (0.7%) 1 6/143 (4.2%) 6 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Leukocytosis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Neutropenia 0/153 (0%) 0 3/143 (2.1%) 3 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Thrombocytopenia 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Acute myocardial infarction 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Angina pectoris 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Atrial fibrillation 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cardiac arrest 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Myocardial infarction 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Supraventricular tachycardia 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Endocrine disorders
    Addison's disease 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Adrenal insufficiency 2/153 (1.3%) 2 0/143 (0%) 0 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Adrenocortical insufficiency acute 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Autoimmune thyroiditis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Eye disorders
    Angle closure glaucoma 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Vision blurred 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 7/153 (4.6%) 9 2/143 (1.4%) 2 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Abdominal pain upper 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Anal fistula 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Autoimmune colitis 2/153 (1.3%) 2 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Colitis 3/153 (2%) 3 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Constipation 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Diarrhoea 4/153 (2.6%) 4 9/143 (6.3%) 9 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Diarrhoea haemorrhagic 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Diverticular perforation 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Duodenal perforation 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Duodenal ulcer 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Faecaloma 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastritis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal haemorrhage 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal inflammation 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Ileus 1/153 (0.7%) 1 3/143 (2.1%) 3 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Impaired gastric emptying 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Intestinal obstruction 2/153 (1.3%) 2 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Intestinal perforation 0/153 (0%) 0 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Intra-abdominal haemorrhage 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Large intestinal obstruction 1/153 (0.7%) 1 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Large intestine perforation 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pancreatitis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Short-bowel syndrome 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Small intestinal obstruction 2/153 (1.3%) 2 5/143 (3.5%) 9 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Subileus 2/153 (1.3%) 2 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Upper gastrointestinal haemorrhage 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Vomiting 1/153 (0.7%) 1 4/143 (2.8%) 4 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    General disorders
    Asthenia 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Chest pain 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Death 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Device related thrombosis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Fatigue 0/153 (0%) 0 3/143 (2.1%) 3 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gait disturbance 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    General physical health deterioration 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Mucosal inflammation 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Oedema peripheral 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pyrexia 4/153 (2.6%) 4 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hepatobiliary disorders
    Acute hepatic failure 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Autoimmune hepatitis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Bile duct stenosis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Biliary dilatation 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cholangitis 0/153 (0%) 0 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cholangitis acute 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Cholecystitis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cholecystitis acute 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cholestasis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hepatic failure 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Hepatitis 2/153 (1.3%) 2 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Immune-mediated hepatitis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Jaundice cholestatic 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Immune system disorders
    Cytokine release syndrome 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Hypersensitivity 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Infections and infestations
    Abdominal sepsis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    COVID-19 0/153 (0%) 0 0/143 (0%) 0 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Cellulitis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cholecystitis infective 0/153 (0%) 0 1/143 (0.7%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Clostridium difficile colitis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Clostridium difficile infection 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Device related infection 0/153 (0%) 0 2/143 (1.4%) 3 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Diverticulitis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Endophthalmitis 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Escherichia pyelonephritis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Escherichia sepsis 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Gastroenteritis 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal infection 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Infection 2/153 (1.3%) 3 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Influenza 1/153 (0.7%) 1 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Lower respiratory tract infection 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Lymph gland infection 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Meningoencephalitis viral 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Pelvic infection 0/153 (0%) 0 1/143 (0.7%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pneumonia 3/153 (2%) 3 2/143 (1.4%) 2 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Pneumonia streptococcal 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pyelonephritis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pyelonephritis acute 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Respiratory tract infection 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Sepsis 0/153 (0%) 0 1/143 (0.7%) 1 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Stoma site abscess 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Stoma site infection 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Urinary tract infection 0/153 (0%) 0 1/143 (0.7%) 1 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Urosepsis 0/153 (0%) 0 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Vascular device infection 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Viral infection 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal stoma complication 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Head injury 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hip fracture 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Stoma site haemorrhage 0/153 (0%) 0 1/143 (0.7%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Subdural haematoma 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Tibia fracture 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Urinary tract stoma complication 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Investigations
    Liver function test increased 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Neutrophil count decreased 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Norovirus test positive 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/153 (0%) 0 3/143 (2.1%) 3 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Dehydration 0/153 (0%) 0 4/143 (2.8%) 7 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Failure to thrive 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hyperglycaemia 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hypoalbuminaemia 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Hypoglycaemia 0/153 (0%) 0 0/143 (0%) 0 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Hypokalaemia 0/153 (0%) 0 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hypomagnesaemia 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hyponatraemia 1/153 (0.7%) 1 1/143 (0.7%) 1 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Type 2 diabetes mellitus 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Autoimmune arthritis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Back pain 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Myositis 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Pain in jaw 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/153 (0.7%) 1 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Bladder neoplasm 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Breast cancer 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cancer pain 1/153 (0.7%) 2 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Infected neoplasm 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Lung carcinoma cell type unspecified recurrent 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Oropharyngeal cancer 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Rectal adenoma 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Rectal neoplasm 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Squamous cell carcinoma 2/153 (1.3%) 4 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Tumour associated fever 0/153 (0%) 0 2/143 (1.4%) 2 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Vaginal neoplasm 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Nervous system disorders
    Amnesia 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Aphasia 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Carotid artery stenosis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cerebral infarction 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cerebral ischaemia 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Cerebrovascular accident 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Occipital neuralgia 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pseudobulbar palsy 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Syncope 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Transient ischaemic attack 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Psychiatric disorders
    Confusional state 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Depression 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Suicide attempt 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 3/153 (2%) 3 2/143 (1.4%) 2 3/56 (5.4%) 3 0/8 (0%) 0 1/4 (25%) 1
    Autoimmune nephritis 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Glomerulonephritis 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hydronephrosis 1/153 (0.7%) 1 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Prerenal failure 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Renal failure 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Renal impairment 1/153 (0.7%) 2 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Chronic obstructive pulmonary disease 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Dyspnoea 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hyperventilation 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Interstitial lung disease 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Pneumonitis 1/153 (0.7%) 1 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Pulmonary embolism 1/153 (0.7%) 1 4/143 (2.8%) 4 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Respiratory failure 0/153 (0%) 0 0/143 (0%) 0 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Skin and subcutaneous tissue disorders
    Diabetic foot 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Rash 1/153 (0.7%) 1 0/143 (0%) 0 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Skin erosion 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Skin ulcer 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Vascular disorders
    Aortic dissection 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Deep vein thrombosis 1/153 (0.7%) 1 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Embolism 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hypertension 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Superior vena cava syndrome 0/153 (0%) 0 1/143 (0.7%) 1 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Other (Not Including Serious) Adverse Events
    Pembrolizumab First Course Standard of Care (SOC) First Course SOC Switched Over to Pembrolizumab Pembrolizumab-Second Course SOC Switched Over to Pembrolizumab-Second Course
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 145/153 (94.8%) 142/143 (99.3%) 52/56 (92.9%) 8/8 (100%) 2/4 (50%)
    Blood and lymphatic system disorders
    Anaemia 26/153 (17%) 32 32/143 (22.4%) 39 8/56 (14.3%) 17 0/8 (0%) 0 0/4 (0%) 0
    Leukopenia 0/153 (0%) 0 3/143 (2.1%) 12 0/56 (0%) 0 0/8 (0%) 0 1/4 (25%) 1
    Neutropenia 3/153 (2%) 4 27/143 (18.9%) 52 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Thrombocytopenia 1/153 (0.7%) 1 8/143 (5.6%) 18 0/56 (0%) 0 0/8 (0%) 0 1/4 (25%) 1
    Cardiac disorders
    Atrial fibrillation 3/153 (2%) 3 2/143 (1.4%) 2 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Endocrine disorders
    Hyperthyroidism 6/153 (3.9%) 6 0/143 (0%) 0 5/56 (8.9%) 5 1/8 (12.5%) 1 0/4 (0%) 0
    Hypothyroidism 19/153 (12.4%) 20 4/143 (2.8%) 6 7/56 (12.5%) 7 2/8 (25%) 2 0/4 (0%) 0
    Eye disorders
    Dry eye 9/153 (5.9%) 11 3/143 (2.1%) 4 0/56 (0%) 0 1/8 (12.5%) 2 0/4 (0%) 0
    Vision blurred 8/153 (5.2%) 8 2/143 (1.4%) 2 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 34/153 (22.2%) 56 40/143 (28%) 61 8/56 (14.3%) 12 0/8 (0%) 0 0/4 (0%) 0
    Abdominal pain upper 19/153 (12.4%) 21 11/143 (7.7%) 14 2/56 (3.6%) 3 1/8 (12.5%) 1 0/4 (0%) 0
    Ascites 1/153 (0.7%) 1 3/143 (2.1%) 3 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Constipation 26/153 (17%) 30 45/143 (31.5%) 76 13/56 (23.2%) 19 0/8 (0%) 0 0/4 (0%) 0
    Diarrhoea 65/153 (42.5%) 107 88/143 (61.5%) 203 17/56 (30.4%) 35 1/8 (12.5%) 5 0/4 (0%) 0
    Dry mouth 17/153 (11.1%) 18 9/143 (6.3%) 10 3/56 (5.4%) 4 1/8 (12.5%) 1 0/4 (0%) 0
    Dyspepsia 9/153 (5.9%) 10 16/143 (11.2%) 21 5/56 (8.9%) 7 0/8 (0%) 0 0/4 (0%) 0
    Haemorrhoids 2/153 (1.3%) 2 10/143 (7%) 10 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Nausea 47/153 (30.7%) 69 85/143 (59.4%) 283 16/56 (28.6%) 23 1/8 (12.5%) 1 0/4 (0%) 0
    Stomatitis 10/153 (6.5%) 11 43/143 (30.1%) 75 4/56 (7.1%) 4 0/8 (0%) 0 0/4 (0%) 0
    Vomiting 33/153 (21.6%) 53 53/143 (37.1%) 84 12/56 (21.4%) 20 0/8 (0%) 0 0/4 (0%) 0
    General disorders
    Asthenia 19/153 (12.4%) 32 30/143 (21%) 57 5/56 (8.9%) 8 1/8 (12.5%) 1 0/4 (0%) 0
    Chest pain 8/153 (5.2%) 9 3/143 (2.1%) 4 4/56 (7.1%) 5 0/8 (0%) 0 0/4 (0%) 0
    Fatigue 58/153 (37.9%) 79 70/143 (49%) 177 9/56 (16.1%) 9 2/8 (25%) 2 0/4 (0%) 0
    Influenza like illness 14/153 (9.2%) 20 4/143 (2.8%) 4 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Malaise 10/153 (6.5%) 11 6/143 (4.2%) 8 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Mucosal inflammation 7/153 (4.6%) 7 27/143 (18.9%) 49 2/56 (3.6%) 2 1/8 (12.5%) 1 0/4 (0%) 0
    Oedema peripheral 18/153 (11.8%) 24 11/143 (7.7%) 13 10/56 (17.9%) 11 0/8 (0%) 0 0/4 (0%) 0
    Peripheral swelling 4/153 (2.6%) 5 0/143 (0%) 0 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Pyrexia 24/153 (15.7%) 29 20/143 (14%) 28 6/56 (10.7%) 7 0/8 (0%) 0 0/4 (0%) 0
    Temperature intolerance 1/153 (0.7%) 2 8/143 (5.6%) 12 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Infections and infestations
    Cystitis 4/153 (2.6%) 4 5/143 (3.5%) 8 4/56 (7.1%) 6 0/8 (0%) 0 0/4 (0%) 0
    Influenza 7/153 (4.6%) 8 4/143 (2.8%) 4 1/56 (1.8%) 1 1/8 (12.5%) 1 0/4 (0%) 0
    Nasopharyngitis 20/153 (13.1%) 31 10/143 (7%) 13 8/56 (14.3%) 12 0/8 (0%) 0 0/4 (0%) 0
    Oral candidiasis 3/153 (2%) 4 6/143 (4.2%) 6 4/56 (7.1%) 5 0/8 (0%) 0 0/4 (0%) 0
    Paronychia 1/153 (0.7%) 1 8/143 (5.6%) 17 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Tooth infection 8/153 (5.2%) 9 5/143 (3.5%) 5 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Upper respiratory tract infection 16/153 (10.5%) 17 8/143 (5.6%) 11 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Urinary tract infection 14/153 (9.2%) 19 15/143 (10.5%) 23 7/56 (12.5%) 9 0/8 (0%) 0 0/4 (0%) 0
    Injury, poisoning and procedural complications
    Fall 11/153 (7.2%) 13 5/143 (3.5%) 5 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Investigations
    Alanine aminotransferase increased 22/153 (14.4%) 33 16/143 (11.2%) 30 5/56 (8.9%) 6 0/8 (0%) 0 0/4 (0%) 0
    Aspartate aminotransferase increased 24/153 (15.7%) 33 12/143 (8.4%) 24 6/56 (10.7%) 6 0/8 (0%) 0 0/4 (0%) 0
    Blood alkaline phosphatase increased 22/153 (14.4%) 30 6/143 (4.2%) 9 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Gamma-glutamyltransferase increased 8/153 (5.2%) 8 3/143 (2.1%) 5 1/56 (1.8%) 2 0/8 (0%) 0 0/4 (0%) 0
    Neutrophil count decreased 2/153 (1.3%) 2 32/143 (22.4%) 64 1/56 (1.8%) 6 0/8 (0%) 0 0/4 (0%) 0
    Platelet count decreased 2/153 (1.3%) 4 10/143 (7%) 28 2/56 (3.6%) 3 0/8 (0%) 0 0/4 (0%) 0
    Weight decreased 7/153 (4.6%) 7 17/143 (11.9%) 17 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    White blood cell count decreased 1/153 (0.7%) 1 17/143 (11.9%) 47 1/56 (1.8%) 3 0/8 (0%) 0 0/4 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 36/153 (23.5%) 49 57/143 (39.9%) 114 2/56 (3.6%) 2 1/8 (12.5%) 1 0/4 (0%) 0
    Dehydration 11/153 (7.2%) 11 7/143 (4.9%) 7 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Hyperglycaemia 8/153 (5.2%) 24 4/143 (2.8%) 4 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hypoalbuminaemia 5/153 (3.3%) 5 8/143 (5.6%) 17 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Hypokalaemia 13/153 (8.5%) 25 23/143 (16.1%) 38 2/56 (3.6%) 4 0/8 (0%) 0 0/4 (0%) 0
    Hyponatraemia 10/153 (6.5%) 11 6/143 (4.2%) 7 3/56 (5.4%) 4 1/8 (12.5%) 1 0/4 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 31/153 (20.3%) 52 10/143 (7%) 11 11/56 (19.6%) 17 0/8 (0%) 0 0/4 (0%) 0
    Back pain 25/153 (16.3%) 29 24/143 (16.8%) 27 11/56 (19.6%) 13 1/8 (12.5%) 1 0/4 (0%) 0
    Muscle spasms 8/153 (5.2%) 9 5/143 (3.5%) 7 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Muscular weakness 5/153 (3.3%) 7 1/143 (0.7%) 1 3/56 (5.4%) 3 1/8 (12.5%) 1 0/4 (0%) 0
    Myalgia 8/153 (5.2%) 9 12/143 (8.4%) 15 2/56 (3.6%) 6 0/8 (0%) 0 0/4 (0%) 0
    Neck pain 4/153 (2.6%) 5 5/143 (3.5%) 5 1/56 (1.8%) 1 1/8 (12.5%) 1 0/4 (0%) 0
    Pain in extremity 18/153 (11.8%) 21 11/143 (7.7%) 11 6/56 (10.7%) 7 1/8 (12.5%) 1 0/4 (0%) 0
    Nervous system disorders
    Dizziness 24/153 (15.7%) 29 27/143 (18.9%) 54 5/56 (8.9%) 9 1/8 (12.5%) 1 0/4 (0%) 0
    Dysgeusia 5/153 (3.3%) 5 13/143 (9.1%) 14 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Headache 21/153 (13.7%) 26 22/143 (15.4%) 37 16/56 (28.6%) 25 0/8 (0%) 0 0/4 (0%) 0
    Neuropathy peripheral 1/153 (0.7%) 1 28/143 (19.6%) 41 4/56 (7.1%) 4 0/8 (0%) 0 0/4 (0%) 0
    Paraesthesia 6/153 (3.9%) 7 8/143 (5.6%) 10 1/56 (1.8%) 1 1/8 (12.5%) 1 0/4 (0%) 0
    Peripheral sensory neuropathy 3/153 (2%) 3 31/143 (21.7%) 51 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Psychiatric disorders
    Anger 0/153 (0%) 0 0/143 (0%) 0 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Anxiety 9/153 (5.9%) 11 4/143 (2.8%) 6 4/56 (7.1%) 4 0/8 (0%) 0 0/4 (0%) 0
    Depression 7/153 (4.6%) 7 5/143 (3.5%) 5 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Discouragement 0/153 (0%) 0 0/143 (0%) 0 0/56 (0%) 0 1/8 (12.5%) 1 0/4 (0%) 0
    Insomnia 12/153 (7.8%) 14 10/143 (7%) 11 7/56 (12.5%) 7 0/8 (0%) 0 0/4 (0%) 0
    Renal and urinary disorders
    Proteinuria 5/153 (3.3%) 7 10/143 (7%) 27 2/56 (3.6%) 5 0/8 (0%) 0 0/4 (0%) 0
    Renal impairment 1/153 (0.7%) 1 0/143 (0%) 0 1/56 (1.8%) 1 1/8 (12.5%) 1 0/4 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 26/153 (17%) 31 23/143 (16.1%) 26 7/56 (12.5%) 9 1/8 (12.5%) 1 0/4 (0%) 0
    Dysphonia 2/153 (1.3%) 2 8/143 (5.6%) 9 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Dyspnoea 20/153 (13.1%) 25 15/143 (10.5%) 22 6/56 (10.7%) 8 1/8 (12.5%) 1 0/4 (0%) 0
    Epistaxis 2/153 (1.3%) 3 23/143 (16.1%) 30 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Hiccups 2/153 (1.3%) 3 8/143 (5.6%) 10 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Oropharyngeal pain 4/153 (2.6%) 4 8/143 (5.6%) 8 3/56 (5.4%) 3 0/8 (0%) 0 0/4 (0%) 0
    Productive cough 8/153 (5.2%) 8 6/143 (4.2%) 7 5/56 (8.9%) 6 0/8 (0%) 0 0/4 (0%) 0
    Rhinorrhoea 9/153 (5.9%) 10 13/143 (9.1%) 15 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 11/153 (7.2%) 11 29/143 (20.3%) 32 0/56 (0%) 0 0/8 (0%) 0 0/4 (0%) 0
    Dermatitis acneiform 3/153 (2%) 6 8/143 (5.6%) 22 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Dry skin 19/153 (12.4%) 21 14/143 (9.8%) 15 9/56 (16.1%) 11 3/8 (37.5%) 3 1/4 (25%) 1
    Palmar-plantar erythrodysaesthesia syndrome 1/153 (0.7%) 1 25/143 (17.5%) 35 1/56 (1.8%) 1 0/8 (0%) 0 0/4 (0%) 0
    Pruritus 25/153 (16.3%) 37 12/143 (8.4%) 15 14/56 (25%) 23 0/8 (0%) 0 0/4 (0%) 0
    Rash 19/153 (12.4%) 27 16/143 (11.2%) 22 10/56 (17.9%) 12 2/8 (25%) 3 0/4 (0%) 0
    Rash maculo-papular 8/153 (5.2%) 9 3/143 (2.1%) 3 2/56 (3.6%) 2 0/8 (0%) 0 0/4 (0%) 0
    Skin hyperpigmentation 0/153 (0%) 0 8/143 (5.6%) 10 1/56 (1.8%) 2 0/8 (0%) 0 0/4 (0%) 0
    Vascular disorders
    Hypertension 19/153 (12.4%) 25 16/143 (11.2%) 23 1/56 (1.8%) 1 0/8 (0%) 0 1/4 (25%) 1
    Hypotension 4/153 (2.6%) 4 3/143 (2.1%) 3 5/56 (8.9%) 5 0/8 (0%) 0 0/4 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme LLC
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02563002
    Other Study ID Numbers:
    • 3475-177
    • 2015-002024-89
    • 163238
    • MK-3475-177
    • KEYNOTE-177
    First Posted:
    Sep 29, 2015
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022