Study of Pembrolizumab (MK-3475) in Participants With Advanced Urothelial Cancer (MK-3475-052/KEYNOTE-052)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02335424
Collaborator
(none)
374
1
83.8

Study Details

Study Description

Brief Summary

This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study objective is to determine the objective response rate (ORR) in all participants and by programmed cell death ligand 1 (PD-L1) status.

With Amendment 4, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

Condition or Disease Intervention/Treatment Phase
  • Biological: pembrolizumab
Phase 2

Detailed Description

Participants receiving pembrolizumab who attain a complete response (CR) may consider stopping trial treatment if they meet criteria for holding therapy. Participants who stop trial treatment after receiving 24 months of trial treatment for reasons other than progressive disease (PD) or intolerability, or participants who attain a CR and stop trial treatment may be eligible for up to one year of retreatment upon experiencing PD.

Study Design

Study Type:
Interventional
Actual Enrollment :
374 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects With Advanced/Unresectable or Metastatic Urothelial Cancer
Actual Study Start Date :
Feb 24, 2015
Actual Primary Completion Date :
Jun 19, 2018
Actual Study Completion Date :
Feb 18, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab

Participants receive pembrolizumab, 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to 24 months.

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
  • Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in all participants and was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.

    2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per RECIST 1.1 is presented.

    3. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 strong positive expression of ≥10% CPS and experienced a CR or PR per RECIST 1.1 is presented.

    Secondary Outcome Measures

    1. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented.

    2. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS and who had a confirmed CR or PR is presented.

    3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS and who had a confirmed CR or PR is presented.

    4. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      PFS was determined in all participants. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants is presented.

    5. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.

    6. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.

    7. Overall Survival (OS) in All Participants [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants is presented.

    8. Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.

    9. Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)]

      OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.

    10. Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants [Month 6]

      The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

    11. Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Month 6]

      The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

    12. Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Month 6]

      The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.

    13. Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants [Month 12]

      The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

    14. Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Month 12]

      The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

    15. Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Month 12]

      The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.

    16. Overall Survival Rate (OS Rate) at Month 6 in All Participants [Month 6]

      The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

    17. Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Month 6]

      The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

    18. Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Month 6]

      The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.

    19. Overall Survival Rate (OS Rate) at Month 12 in All Participants [Month 12]

      The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

    20. Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Month 12]

      The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

    21. Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Month 12]

      The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.

    22. Programmed Cell Death Ligand 1 (PD-L1) Expression Status [Day 1]

      PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of <1% = negative; ≥1% = positive; and ≥10% = strongly positive. The number of participants categorized by PD-L1 CPS score is presented.

    23. Number of Participants Who Experienced At Least One Adverse Event (AE) [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing 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 is presented. These safety results are based on a 26-September-2018 data cutoff date.

    24. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing 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 is presented. These results are based on a 26-September-2018 data cutoff date.

    Other Outcome Measures

    1. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per modified RECIST is presented.

    2. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1% [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per modified RECIST is presented.

    3. Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10% [Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)]

      ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥10% CPS and experienced a CR or PR per modified RECIST is presented.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically- or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies)

    • Ineligible for cisplatin therapy

    • No prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant platinum-based chemotherapy with recurrence >12 months since completion of therapy is allowed)

    • Available tissue from a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

    • Measureable disease

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

    • Adequate organ function

    • Female participants of childbearing potential have a negative urine or serum pregnancy test; surgically sterile, or willing to use 2 acceptable methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment

    • Male participants must be willing to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment

    Exclusion Criteria:
    • Disease that is suitable for local therapy administered with curative intent

    • Currently participating or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study treatment

    • Prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier

    • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent

    • Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancer

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

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

    • Evidence of interstitial lung disease or active non-infectious pneumonitis

    • Active infection requiring systemic therapy

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

    • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor

    • Known human immunodeficiency virus (HIV)

    • Known active Hepatitis B or C

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

    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:
    NCT02335424
    Other Study ID Numbers:
    • 3475-052
    • MK-3475-052
    • KEYNOTE-052
    • 2014-002206-20
    First Posted:
    Jan 9, 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 These interim results are based on a database cutoff date of 26-September-2018, at which time 89 participants were ongoing in the study.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 24 months
    Period Title: Overall Study
    STARTED 374
    Treated 370
    COMPLETED 0
    NOT COMPLETED 374

    Baseline Characteristics

    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Overall Participants 370
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    73.0
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    84
    22.7%
    Male
    286
    77.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    0.5%
    Asian
    26
    7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    8
    2.2%
    White
    328
    88.6%
    More than one race
    2
    0.5%
    Unknown or Not Reported
    4
    1.1%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
    Description ORR was determined in all participants and was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    28.6
    7.7%
    2. Primary Outcome
    Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per RECIST 1.1 is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    32.3
    8.7%
    3. Primary Outcome
    Title Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed 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) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 strong positive expression of ≥10% CPS and experienced a CR or PR per RECIST 1.1 is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    47.3
    12.8%
    4. Secondary Outcome
    Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
    Description DOR was determined in participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a confirmed CR or PR is presented.
    Time Frame From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and who had a confirmed CR or confirmed PR.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 106
    Median (Full Range) [Months]
    30.1
    5. Secondary Outcome
    Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description DOR was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS and who had a confirmed CR or PR is presented.
    Time Frame From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment, had a PD-L1 positive expression of ≥1% CPS, and who had a confirmed CR or PR.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 91
    Median (Full Range) [Months]
    30.1
    6. Secondary Outcome
    Title Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description DOR was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, and had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% relative increase in the sum of diameters of target lesions. In addition, the sum must also have an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. The DOR per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS and who had a confirmed CR or PR is presented.
    Time Frame From time of first documented evidence of CR or PR through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment, had a PD-L1 strong positive expression of ≥10% CPS, and who had a confirmed CR or PR.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 52
    Median (Full Range) [Months]
    NA
    7. Secondary Outcome
    Title Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
    Description PFS was determined in all participants. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Median (95% Confidence Interval) [Months]
    2.2
    8. Secondary Outcome
    Title Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description PFS was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Median (95% Confidence Interval) [Months]
    3.4
    9. Secondary Outcome
    Title Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description PFS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS per RECIST 1.1 for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Median (95% Confidence Interval) [Months]
    4.9
    10. Secondary Outcome
    Title Overall Survival (OS) in All Participants
    Description OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Median (95% Confidence Interval) [Months]
    11.3
    11. Secondary Outcome
    Title Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description OS was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 positive expression of ≥1% CPS is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Median (95% Confidence Interval) [Months]
    12.4
    12. Secondary Outcome
    Title Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description OS was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS for all participants who had a PD-L1 strong positive expression of ≥10% CPS is presented.
    Time Frame Through database cutoff date of 26-Sep-2018 (Up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Median (95% Confidence Interval) [Months]
    18.5
    13. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants
    Description The PFS rate was determined in all participants at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    33.4
    9%
    14. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    37.2
    10.1%
    15. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    49.0
    13.2%
    16. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants
    Description The PFS rate was determined in all participants at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    22.0
    5.9%
    17. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description The PFS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    24.7
    6.7%
    18. Secondary Outcome
    Title Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description The PFS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR). Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Time to scheduled tumor assessment visit rather than the actual tumor assessment visit was used in the analysis. Participants were censored at the date of their last assessment. The PFS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    38.6
    10.4%
    19. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 6 in All Participants
    Description The OS rate was determined for all participants at Month 6 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    67.0
    18.1%
    20. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    71.3
    19.3%
    21. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 6. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 6 was calculated.
    Time Frame Month 6

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    76.3
    20.6%
    22. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 12 in All Participants
    Description The OS rate was determined for all participants at Month 12 and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    46.9
    12.7%
    23. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description The OS rate was determined in participants who had a PD-L1 CPS of ≥1%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    50.9
    13.8%
    24. Secondary Outcome
    Title Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description The OS rate was determined in participants who had a PD-L1 CPS of ≥10%, as measured by immunohistochemistry assay, at Month 12. OS was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last assessment. The OS rate at Month 12 was calculated.
    Time Frame Month 12

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 strong positive expression of ≥10% CPS.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    60.7
    16.4%
    25. Secondary Outcome
    Title Programmed Cell Death Ligand 1 (PD-L1) Expression Status
    Description PD-L1 expression status was determined as the percent of disease tumor cells, from newly obtained tumor biopsies, demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. The assay uses a Combined Positive Score (CPS) as a measure of PD-L1 positivity. The CPS is calculated as the number of PD-L1-positive cells divided by the number of viable tumor cells analyzed multiplied by 100. A CPS of <1% = negative; ≥1% = positive; and ≥10% = strongly positive. The number of participants categorized by PD-L1 CPS score is presented.
    Time Frame Day 1

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    PD-L1 CPS <1%
    79
    21.4%
    PD-L1 CPS ≥1% to <10%
    172
    46.5%
    PD-L1 CPS ≥10%
    110
    29.7%
    Unknown
    9
    2.4%
    26. Secondary Outcome
    Title Number of Participants Who Experienced At Least One Adverse Event (AE)
    Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing 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 is presented. These safety results are based on a 26-September-2018 data cutoff date.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Count of Participants [Participants]
    361
    97.6%
    27. Secondary Outcome
    Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
    Description An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing 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 is presented. These results are based on a 26-September-2018 data cutoff date.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Count of Participants [Participants]
    61
    16.5%
    28. Other Pre-specified Outcome
    Title Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in All Participants
    Description ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR per modified RECIST is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 370
    Number (95% Confidence Interval) [Percentage of participants]
    30.5
    8.2%
    29. Other Pre-specified Outcome
    Title Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
    Description ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per modified RECIST is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥1% CPS
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 282
    Number (95% Confidence Interval) [Percentage of participants]
    34.4
    9.3%
    30. Other Pre-specified Outcome
    Title Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
    Description ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: complete disappearance of all lesions and no new lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per modified RECIST as assessed by Blinded Independent Central Review (BICR). Modified RECIST differs from RECIST 1.1 in that progressive disease requires confirmation by a repeat radiological assessment no less than 4 weeks from the date of first documented progressive disease. Participants with missing data were considered non-responders. The percentage of participants who had a PD-L1 positive expression of ≥10% CPS and experienced a CR or PR per modified RECIST is presented.
    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study treatment and had a PD-L1 positive expression of ≥10% CPS
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    Measure Participants 110
    Number (95% Confidence Interval) [Percentage of participants]
    49.1
    13.3%

    Adverse Events

    Time Frame Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 months)
    Adverse Event Reporting Description Population: All participants who received at least one dose of study treatment. Per protocol, progression of cancer under study was not considered an adverse event (AE) unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs.
    Arm/Group Title Pembrolizumab 200 mg
    Arm/Group Description Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for up to 24 months
    All Cause Mortality
    Pembrolizumab 200 mg
    Affected / at Risk (%) # Events
    Total 239/370 (64.6%)
    Serious Adverse Events
    Pembrolizumab 200 mg
    Affected / at Risk (%) # Events
    Total 190/370 (51.4%)
    Blood and lymphatic system disorders
    Anaemia 6/370 (1.6%) 6
    Febrile neutropenia 1/370 (0.3%) 1
    Immune thrombocytopenic purpura 1/370 (0.3%) 1
    Thrombocytopenia 1/370 (0.3%) 1
    Cardiac disorders
    Acute myocardial infarction 2/370 (0.5%) 2
    Angina pectoris 2/370 (0.5%) 2
    Atrial fibrillation 1/370 (0.3%) 1
    Atrioventricular block 1/370 (0.3%) 1
    Ischaemic cardiomyopathy 1/370 (0.3%) 1
    Left ventricular failure 1/370 (0.3%) 1
    Myocardial infarction 2/370 (0.5%) 2
    Myocarditis 2/370 (0.5%) 2
    Pericarditis 1/370 (0.3%) 1
    Supraventricular tachycardia 1/370 (0.3%) 1
    Endocrine disorders
    Addison's disease 2/370 (0.5%) 2
    Adrenal insufficiency 5/370 (1.4%) 5
    Hypophysitis 1/370 (0.3%) 1
    Hypopituitarism 1/370 (0.3%) 1
    Thyroiditis 1/370 (0.3%) 1
    Gastrointestinal disorders
    Abdominal pain lower 1/370 (0.3%) 1
    Ascites 1/370 (0.3%) 1
    Colitis 2/370 (0.5%) 2
    Constipation 4/370 (1.1%) 4
    Diarrhoea 5/370 (1.4%) 5
    Duodenal obstruction 1/370 (0.3%) 1
    Gastrointestinal haemorrhage 1/370 (0.3%) 1
    Gastrointestinal motility disorder 1/370 (0.3%) 1
    Ileus 3/370 (0.8%) 3
    Intestinal ischaemia 1/370 (0.3%) 1
    Intestinal obstruction 3/370 (0.8%) 3
    Large intestinal obstruction 1/370 (0.3%) 1
    Large intestine perforation 1/370 (0.3%) 1
    Nausea 1/370 (0.3%) 1
    Pancreatitis acute 1/370 (0.3%) 1
    Proctitis 1/370 (0.3%) 1
    Rectal haemorrhage 1/370 (0.3%) 1
    Small intestinal obstruction 3/370 (0.8%) 3
    Vomiting 1/370 (0.3%) 1
    General disorders
    Asthenia 2/370 (0.5%) 2
    Cardiac complication associated with device 1/370 (0.3%) 1
    Death 3/370 (0.8%) 3
    Fatigue 1/370 (0.3%) 1
    General physical health deterioration 1/370 (0.3%) 1
    Multiple organ dysfunction syndrome 1/370 (0.3%) 1
    Oedema peripheral 2/370 (0.5%) 2
    Pyrexia 5/370 (1.4%) 5
    Hepatobiliary disorders
    Autoimmune hepatitis 2/370 (0.5%) 2
    Cholecystitis 1/370 (0.3%) 2
    Drug-induced liver injury 1/370 (0.3%) 1
    Hepatitis 2/370 (0.5%) 2
    Liver injury 1/370 (0.3%) 1
    Infections and infestations
    Abscess neck 1/370 (0.3%) 1
    Acute sinusitis 1/370 (0.3%) 1
    Atypical pneumonia 1/370 (0.3%) 1
    Bronchitis 1/370 (0.3%) 1
    Candida infection 1/370 (0.3%) 1
    Cellulitis 3/370 (0.8%) 3
    Clostridium difficile infection 2/370 (0.5%) 2
    Diverticulitis 2/370 (0.5%) 2
    Escherichia sepsis 2/370 (0.5%) 2
    Gastroenteritis 1/370 (0.3%) 1
    Infected skin ulcer 1/370 (0.3%) 1
    Influenza 2/370 (0.5%) 2
    Kidney infection 2/370 (0.5%) 2
    Lower respiratory tract infection 1/370 (0.3%) 1
    Lung infection 1/370 (0.3%) 1
    Pneumonia 14/370 (3.8%) 14
    Pyelonephritis 3/370 (0.8%) 3
    Pyelonephritis acute 1/370 (0.3%) 1
    Renal abscess 1/370 (0.3%) 1
    Respiratory tract infection 2/370 (0.5%) 2
    Sepsis 9/370 (2.4%) 9
    Septic shock 1/370 (0.3%) 1
    Upper respiratory tract infection 2/370 (0.5%) 2
    Urinary tract infection 26/370 (7%) 31
    Urosepsis 14/370 (3.8%) 14
    Injury, poisoning and procedural complications
    Fall 1/370 (0.3%) 1
    Femur fracture 4/370 (1.1%) 4
    Incisional hernia 1/370 (0.3%) 1
    Injury 1/370 (0.3%) 1
    Intentional overdose 1/370 (0.3%) 1
    Overdose 1/370 (0.3%) 1
    Stoma obstruction 1/370 (0.3%) 1
    Urinary tract stoma complication 3/370 (0.8%) 3
    Urostomy complication 1/370 (0.3%) 1
    Investigations
    Alanine aminotransferase increased 1/370 (0.3%) 1
    Aspartate aminotransferase increased 1/370 (0.3%) 1
    Blood creatinine increased 1/370 (0.3%) 1
    Metabolism and nutrition disorders
    Dehydration 4/370 (1.1%) 4
    Diabetic ketoacidosis 2/370 (0.5%) 2
    Gout 1/370 (0.3%) 1
    Hypercalcaemia 4/370 (1.1%) 4
    Hyperkalaemia 2/370 (0.5%) 2
    Hyperuricaemia 1/370 (0.3%) 1
    Hypocalcaemia 1/370 (0.3%) 1
    Hypoglycaemia 1/370 (0.3%) 1
    Hyponatraemia 2/370 (0.5%) 2
    Ketoacidosis 1/370 (0.3%) 1
    Type 1 diabetes mellitus 2/370 (0.5%) 2
    Type 2 diabetes mellitus 1/370 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 2/370 (0.5%) 2
    Autoimmune arthritis 1/370 (0.3%) 2
    Back pain 4/370 (1.1%) 4
    Bone pain 1/370 (0.3%) 1
    Crystal arthropathy 1/370 (0.3%) 1
    Muscular weakness 1/370 (0.3%) 1
    Musculoskeletal pain 1/370 (0.3%) 1
    Myositis 1/370 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 3/370 (0.8%) 3
    Lymphoma 1/370 (0.3%) 1
    Malignant melanoma in situ 1/370 (0.3%) 1
    Malignant neoplasm progression 1/370 (0.3%) 1
    Plasma cell myeloma 1/370 (0.3%) 1
    Squamous cell carcinoma 2/370 (0.5%) 2
    Tumour associated fever 1/370 (0.3%) 1
    Tumour pain 1/370 (0.3%) 1
    Nervous system disorders
    Central nervous system haemorrhage 1/370 (0.3%) 1
    Cerebrovascular accident 3/370 (0.8%) 3
    Encephalopathy 1/370 (0.3%) 1
    Facial paralysis 1/370 (0.3%) 1
    Spinal cord compression 1/370 (0.3%) 1
    Syncope 1/370 (0.3%) 1
    Transient ischaemic attack 1/370 (0.3%) 1
    Product Issues
    Device occlusion 1/370 (0.3%) 1
    Psychiatric disorders
    Delirium 1/370 (0.3%) 1
    Panic attack 1/370 (0.3%) 1
    Renal and urinary disorders
    Acute kidney injury 13/370 (3.5%) 14
    Chronic kidney disease 3/370 (0.8%) 3
    Haematuria 12/370 (3.2%) 13
    Hydronephrosis 2/370 (0.5%) 2
    Renal failure 5/370 (1.4%) 5
    Tubulointerstitial nephritis 2/370 (0.5%) 2
    Urinary incontinence 1/370 (0.3%) 1
    Urinary retention 5/370 (1.4%) 5
    Urinary tract obstruction 2/370 (0.5%) 2
    Respiratory, thoracic and mediastinal disorders
    Aspiration 1/370 (0.3%) 1
    Dyspnoea 5/370 (1.4%) 5
    Hypoxia 1/370 (0.3%) 1
    Pleural effusion 2/370 (0.5%) 2
    Pneumonitis 6/370 (1.6%) 6
    Pneumothorax 1/370 (0.3%) 1
    Pulmonary embolism 3/370 (0.8%) 4
    Respiratory failure 1/370 (0.3%) 1
    Skin and subcutaneous tissue disorders
    Rash pruritic 1/370 (0.3%) 1
    Vascular disorders
    Deep vein thrombosis 2/370 (0.5%) 2
    Embolism 1/370 (0.3%) 1
    Hypertensive crisis 1/370 (0.3%) 1
    Hypovolaemic shock 1/370 (0.3%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab 200 mg
    Affected / at Risk (%) # Events
    Total 340/370 (91.9%)
    Blood and lymphatic system disorders
    Anaemia 73/370 (19.7%) 85
    Endocrine disorders
    Hypothyroidism 42/370 (11.4%) 42
    Gastrointestinal disorders
    Abdominal pain 47/370 (12.7%) 57
    Constipation 87/370 (23.5%) 100
    Diarrhoea 82/370 (22.2%) 123
    Dry mouth 23/370 (6.2%) 23
    Nausea 78/370 (21.1%) 90
    Vomiting 56/370 (15.1%) 79
    General disorders
    Asthenia 45/370 (12.2%) 50
    Chest pain 20/370 (5.4%) 22
    Chills 27/370 (7.3%) 31
    Fatigue 130/370 (35.1%) 158
    Influenza like illness 19/370 (5.1%) 21
    Oedema peripheral 63/370 (17%) 74
    Pyrexia 51/370 (13.8%) 64
    Infections and infestations
    Upper respiratory tract infection 19/370 (5.1%) 23
    Urinary tract infection 75/370 (20.3%) 97
    Injury, poisoning and procedural complications
    Fall 22/370 (5.9%) 26
    Investigations
    Alanine aminotransferase increased 27/370 (7.3%) 31
    Aspartate aminotransferase increased 27/370 (7.3%) 31
    Blood alkaline phosphatase increased 27/370 (7.3%) 30
    Blood creatinine increased 53/370 (14.3%) 67
    Weight decreased 44/370 (11.9%) 47
    Metabolism and nutrition disorders
    Decreased appetite 102/370 (27.6%) 117
    Dehydration 19/370 (5.1%) 19
    Hyperglycaemia 37/370 (10%) 51
    Hyperkalaemia 24/370 (6.5%) 29
    Hypoalbuminaemia 19/370 (5.1%) 26
    Hyponatraemia 41/370 (11.1%) 59
    Musculoskeletal and connective tissue disorders
    Arthralgia 45/370 (12.2%) 60
    Back pain 50/370 (13.5%) 58
    Muscular weakness 26/370 (7%) 29
    Musculoskeletal pain 21/370 (5.7%) 25
    Myalgia 20/370 (5.4%) 22
    Pain in extremity 30/370 (8.1%) 31
    Nervous system disorders
    Dizziness 35/370 (9.5%) 41
    Dysgeusia 22/370 (5.9%) 23
    Headache 20/370 (5.4%) 23
    Psychiatric disorders
    Insomnia 28/370 (7.6%) 28
    Renal and urinary disorders
    Haematuria 53/370 (14.3%) 63
    Proteinuria 21/370 (5.7%) 23
    Respiratory, thoracic and mediastinal disorders
    Cough 76/370 (20.5%) 92
    Dyspnoea 48/370 (13%) 57
    Skin and subcutaneous tissue disorders
    Pruritus 84/370 (22.7%) 108
    Rash 56/370 (15.1%) 79
    Vascular disorders
    Hypertension 20/370 (5.4%) 21

    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:
    NCT02335424
    Other Study ID Numbers:
    • 3475-052
    • MK-3475-052
    • KEYNOTE-052
    • 2014-002206-20
    First Posted:
    Jan 9, 2015
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022