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Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28)

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ClinicalTrials.gov Identifier: NCT02054806
Recruitment Status : Completed
First Posted : February 4, 2014
Results First Posted : October 30, 2023
Last Update Posted : October 30, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumor
Intervention Biological: Pembrolizumab
Enrollment 477
Recruitment Details Participants with a histologically- or cytologically-confirmed diagnosis of 20 advanced (unresectable and/or metastatic) solid tumors, were recruited into a single arm.
Pre-assignment Details

Per protocol, response/progression or adverse events during the second pembrolizumab course were not counted towards efficacy outcome measures or safety outcome measures respectively.

Per protocol, analyses of disease type cohort was planned and conducted for efficacy outcome measures only.
Arm/Group Title Pembrolizumab 10 mg/kg
Hide Arm/Group Description Participants received pembrolizumab 10 mg/kg intravenously (IV) over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. Qualified participants who completed the first course of pembrolizumab treatment but progressed after discontinuation were eligible for a second course of pembrolizumab at 10 mg/kg IV Q2W for up to ~1 additional year, at the Investigator's discretion. Per protocol participants were presented by treatment received in the single arm study.
Period Title: Overall Study
Started 477
Treated During First Course 475
Treated During Second Course 11
Completed 0
Not Completed 477
Reason Not Completed
Sponsor Decision             31
Withdrawal by Subject             43
Protocol Violation             2
Lost to Follow-up             10
Death             391
Arm/Group Title Pembrolizumab (MK-3475) 10 mg/kg
Hide Arm/Group Description Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. Qualified participants who completed the first course of pembrolizumab treatment but progressed after discontinuation were eligible for a second course of pembrolizumab at 10 mg/kg IV Q2W for up to ~1 additional year, at the Investigator's discretion. Per protocol participants were presented by treatment received in the single arm study.
Overall Number of Baseline Participants 475
Hide Baseline Analysis Population Description
The analysis population consisted of all allocated participants who received at least one dose of study drug. Per protocol, Baseline Characteristics were summarized by treatment dose.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 475 participants
58.7  (11.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants
Female
281
  59.2%
Male
194
  40.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants
Hispanic or Latino
18
   3.8%
Not Hispanic or Latino
380
  80.0%
Unknown or Not Reported
77
  16.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 475 participants
American Indian or Alaska Native
1
   0.2%
Asian
99
  20.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
20
   4.2%
White
280
  58.9%
More than one race
2
   0.4%
Unknown or Not Reported
73
  15.4%
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description Overall response rate (ORR) was defined as the percentage of 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 modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator.
Time Frame Up to approximately 86 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least 1 dose of study treatment, had a baseline scan with measurable disease per modified RECIST 1.1 and had the intended indication. Per protocol, participants were analyzed according to disease type.
Arm/Group Title Cohort A1: Colon or Rectal Adenocarcinoma Cohort A2: Anal Canal Squamous Cell Carcinoma Cohort A3: Pancreas Adenocarcinoma Cohort A4: Esophageal Squamous Cell Carcinoma or Adenocarcinoma Cohort A5: Biliary Tract Adenocarcinoma Cohort A6: Carcinoid Tumors Cohort A7: Neuroendocrine Carcinomas Cohort B1: ER Positive HER2 Negative Breast Cancer Cohort B2: Ovarian Epithelial, Fallopian Tube or Primary Peritoneal Carcinoma Cohort B3: Endometrial Carcinoma Cohort B4: Cervical Squamous Cell Cancer Cohort B5: Vulvar Squamous Cell Carcinoma Cohort C1: Small Cell Lung Cancer Cohort C2: Mesothelioma Cohort D1: Thyroid Cancer Cohort D2: Salivary Gland Carcinoma Cohort D3: Nasopharyngeal Carcinoma Cohort E1: Glioblastoma Multiforme Cohort E2: Leiomyosarcoma Cohort E3: Prostate Adenocarcinoma
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with colon or rectal adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with anal canal squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with pancreas adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal (GE) junction).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with biliary tract adenocarcinoma (gallbladder and biliary tree, but excluding ampulla of vater cancers).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with carcinoid tumors.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with estrogen receptor (ER) positive human epidermal growth factor receptor (HER2) negative breast cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ovarian epithelial, fallopian tube or primary peritoneal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with endometrial carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with cervical squamous cell cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with vulvar squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with small cell lung cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with mesothelioma (malignant pleural mesothelioma).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with thyroid cancer (papillary or follicular subtype).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with salivary gland carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with nasopharyngeal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with glioblastoma multiforme.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with leiomyosarcoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with prostate adenocarcinoma.
Overall Number of Participants Analyzed 23 25 24 23 23 25 16 25 26 23 24 18 23 25 22 26 27 25 24 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
4.3
(0.1 to 21.9)
20.0
(6.8 to 40.7)
0.0
(0.0 to 14.2)
30.4
(13.2 to 52.9)
17.4
(5.0 to 38.8)
16.0
(4.5 to 36.1)
6.3
(0.2 to 30.2)
12.0
(2.5 to 31.2)
11.5
(2.4 to 30.2)
13.0
(2.8 to 33.6)
16.7
(4.7 to 37.4)
5.6
(0.1 to 27.3)
34.8
(16.4 to 57.3)
20.0
(6.8 to 40.7)
13.6
(2.9 to 34.9)
11.5
(2.4 to 30.2)
25.9
(11.1 to 46.3)
8.0
(1.0 to 26.0)
4.2
(0.1 to 21.1)
13.0
(2.8 to 33.6)
2.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.
Time Frame Up to approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all allocated participants who received at least one dose of study drug.
Arm/Group Title Pembrolizumab (MK-3475) 10 mg/kg
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg intravenously (IV) over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. Per protocol participants were presented by treatment received in the single arm study.
Overall Number of Participants Analyzed 475
Measure Type: Count of Participants
Unit of Measure: Participants
456
  96.0%
3.Secondary Outcome
Title Number of Participants Who Discontinued From Study Treatment Due to an AE
Hide Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Time Frame Up to approximately 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all allocated participants who received at least one dose of study drug.
Arm/Group Title Pembrolizumab (MK-3475) 10 mg/kg
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg intravenously (IV) over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. Per protocol participants were presented by treatment received in the single arm study.
Overall Number of Participants Analyzed 475
Measure Type: Count of Participants
Unit of Measure: Participants
30
   6.3%
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time from the date of allocation to the date of the first documentation of disease progression, as determined by investigator per modified RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
Time Frame Up to approximately 86 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least 1 dose of study treatment, had a baseline scan with measurable disease per modified RECIST 1.1 and had the intended indication. Per protocol, participants were analyzed according to disease type.
Arm/Group Title Cohort A1: Colon or Rectal Adenocarcinoma Cohort A2: Anal Canal Squamous Cell Carcinoma Cohort A3: Pancreas Adenocarcinoma Cohort A4: Esophageal Squamous Cell Carcinoma or Adenocarcinoma Cohort A5: Biliary Tract Adenocarcinoma Cohort A6: Carcinoid Tumors Cohort A7: Neuroendocrine Carcinomas Cohort B1: ER Positive HER2 Negative Breast Cancer Cohort B2: Ovarian Epithelial, Fallopian Tube or Primary Peritoneal Carcinoma Cohort B3: Endometrial Carcinoma Cohort B4: Cervical Squamous Cell Cancer Cohort B5: Vulvar Squamous Cell Carcinoma Cohort C1: Small Cell Lung Cancer Cohort C2: Mesothelioma Cohort D1: Thyroid Cancer Cohort D2: Salivary Gland Carcinoma Cohort D3: Nasopharyngeal Carcinoma Cohort E1: Glioblastoma Multiforme Cohort E2: Leiomyosarcoma Cohort E3: Prostate Adenocarcinoma
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with colon or rectal adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with anal canal squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with pancreas adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal (GE) junction).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with biliary tract adenocarcinoma (gallbladder and biliary tree, but excluding ampulla of vater cancers).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with carcinoid tumors.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ER positive HER2 negative breast cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ovarian epithelial, fallopian tube or primary peritoneal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with endometrial carcinoma
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with cervical squamous cell cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with vulvar squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with small cell lung cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with mesothelioma (malignant pleural mesothelioma).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with thyroid cancer (papillary or follicular subtype).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with salivary gland carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with nasopharyngeal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with glioblastoma multiforme.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with leiomyosarcoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with prostate adenocarcinoma.
Overall Number of Participants Analyzed 23 25 24 23 23 25 16 25 26 23 24 18 23 25 22 26 27 25 24 23
Median (95% Confidence Interval)
Unit of Measure: Months
1.7
(1.4 to 1.8)
3.1
(1.6 to 6.2)
1.7
(1.5 to 1.8)
1.8
(1.7 to 2.9)
1.8
(1.4 to 2.1)
5.5
(3.5 to 10.7)
4.5
(3.5 to 13.9)
1.8
(1.4 to 3.6)
1.9
(1.8 to 3.5)
1.8
(1.6 to 2.7)
1.8
(1.6 to 3.2)
2.5
(1.4 to 3.7)
1.8
(1.7 to 5.8)
5.5
(3.5 to 8.2)
8.2
(2.2 to 14.4)
3.6
(1.8 to 5.1)
6.4
(3.5 to 13.4)
2.8
(1.9 to 8.1)
2.0
(1.7 to 5.3)
3.5
(1.7 to 6.5)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of allocation to the date of death due to any cause. Participants who were lost to follow-up and those who were alive at the end of the trial were censored at the date of last assessment.
Time Frame Up to approximately 86 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least 1 dose of study treatment, had a baseline scan with measurable disease per modified RECIST 1.1 and had the intended indication. Per protocol, participants were analyzed according to disease type.
Arm/Group Title Cohort A1: Colon or Rectal Adenocarcinoma Cohort A2: Anal Canal Squamous Cell Carcinoma Cohort A3: Pancreas Adenocarcinoma Cohort A4: Esophageal Squamous Cell Carcinoma or Adenocarcinoma Cohort A5: Biliary Tract Adenocarcinoma Cohort A6: Carcinoid Tumors Cohort A7: Neuroendocrine Carcinomas Cohort B1: HR Positive HER2 Negative Breast Cancer Cohort B2: Ovarian Epithelial, Fallopian Tube or Primary Peritoneal Carcinoma Cohort B3: Endometrial Carcinoma Cohort B4: Cervical Squamous Cell Cancer Cohort B5: Vulvar Squamous Cell Carcinoma Cohort C1: Small Cell Lung Cancer Cohort C2: Mesothelioma Cohort D1: Thyroid Cancer Cohort D2: Salivary Gland Carcinoma Cohort D3: Nasopharyngeal Carcinoma Cohort E1: Glioblastoma Multiforme Cohort E2: Leiomyosarcoma Cohort E3: Prostate Adenocarcinoma
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with colon or rectal adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with anal canal squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with Pancreas Adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal (GE) junction).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with biliary tract adenocarcinoma (gallbladder and biliary tree, but excluding ampulla of vater cancers).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with carcinoid tumors.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ER positive HER2 negative breast cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ovarian epithelial, fallopian tube or primary peritoneal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with endometrial carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with cervical squamous cell cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with vulvar squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with small cell lung cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with mesothelioma (malignant pleural mesothelioma).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with thyroid cancer (papillary or follicular subtype).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with salivary gland carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with nasopharyngeal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with glioblastoma multiforme.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with leiomyosarcoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with prostate adenocarcinoma.
Overall Number of Participants Analyzed 23 25 25 23 24 25 16 25 26 24 24 18 23 25 22 26 27 26 24 23
Median (95% Confidence Interval)
Unit of Measure: Months
5.3
(2.2 to 10.9)
8.3
(5.8 to 16.2)
3.9
(2.8 to 5.5)
7.1
(4.3 to 17.7)
5.7
(3.1 to 9.8)
16.2
(7.6 to 22.4)
37.8 [1] 
(20.2 to NA)
8.0
(6.5 to 10.3)
13.1
(7.3 to 18.8)
13.6
(2.2 to 25.2)
10.8
(3.8 to 15.4)
3.7
(3.1 to 7.7)
9.3
(4.1 to 10.6)
18.0
(10.3 to 24.4)
39.7
(29.7 to 65.0)
12.3
(6.0 to 30.1)
16.5
(10.1 to 31.9)
13.1
(8.0 to 26.6)
12.0
(7.7 to 18.3)
7.9
(6.5 to 15.3)
[1]
NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per modified RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per modified RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on investigator with confirmation. The DOR according to modified RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported. Per protocol, participants were analyzed according to disease type.
Time Frame Up to approximately 86 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of all participants who received at least 1 dose of study treatment, had a baseline scan with measurable disease per modified RECIST 1.1, had the intended indication, and experienced a response. Per protocol-specified definition, DOR could not be analyzed in arms which did not have a confirmed response of CR or PR.
Arm/Group Title Cohort A1: Colon or Rectal Adenocarcinoma Cohort A2: Anal Canal Squamous Cell Carcinoma Cohort A3: Pancreas Adenocarcinoma Cohort A4: Esophageal Squamous Cell Carcinoma or Adenocarcinoma Cohort A5: Biliary Tract Adenocarcinoma Cohort A6: Carcinoid Tumors Cohort A7: Neuroendocrine Carcinomas Cohort B1: ER Positive HER2 Negative Breast Cancer Cohort B2: Ovarian Epithelial, Fallopian Tube or Primary Peritoneal Carcinoma Cohort B3: Endometrial Carcinoma Cohort B4: Cervical Squamous Cell Cancer Cohort B5: Vulvar Squamous Cell Carcinoma Cohort C1: Small Cell Lung Cancer Cohort C2: Mesothelioma Cohort D1: Thyroid Cancer Cohort D2: Salivary Gland Carcinoma Cohort D3: Nasopharyngeal Carcinoma Cohort E1: Glioblastoma Multiforme Cohort E2: Leiomyosarcoma Cohort E3: Prostate Adenocarcinoma
Hide Arm/Group Description:
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with colon or rectal adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with anal canal squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with Pancreas Adenocarcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal (GE) junction).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with biliary tract adenocarcinoma (gallbladder and biliary tree, but excluding ampulla of vater cancers).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with carcinoid tumors.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ER positive HER2 negative breast cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with ovarian epithelial, fallopian tube or primary peritoneal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled endometrial carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled cervical squamous cell cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with vulvar squamous cell carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with small cell lung cancer.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with mesothelioma (malignant pleural mesothelioma).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with thyroid cancer (papillary or follicular subtype).
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with salivary gland carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with nasopharyngeal carcinoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with glioblastoma multiforme.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with leiomyosarcoma.
Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. This cohort represents all participants who enrolled with prostate adenocarcinoma.
Overall Number of Participants Analyzed 1 5 0 7 4 4 1 3 3 3 4 1 8 5 3 3 7 2 1 3
Median (Full Range)
Unit of Measure: Months
NA [1] 
(NA to NA)
28.9 [2] 
(3.8 to NA)
14.5 [2] 
(5.6 to NA)
NA [3] 
(6.0 to NA)
10.1 [2] 
(6.9 to NA)
25.1
(25.1 to 25.1)
12.0
(7.4 to 15.9)
37.0 [2] 
(34.4 to NA)
68.5 [2] 
(17.5 to NA)
5.4
(4.1 to 7.5)
3.9
(3.9 to 3.9)
NA [1] 
(NA to NA)
12.0
(3.7 to 44.4)
8.4
(4.6 to 20.3)
3.9
(3.5 to 20.6)
15.0
(4.8 to 34.0)
15.6
(8.3 to 22.8)
12.4
(12.4 to 12.4)
14.2
(13.5 to 31.4)
[1]
NA = Median, upper limit, lower limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.
[2]
NA = Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.
[3]
NA = Median, upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse.
Time Frame Up to ~28 months for first course and up to ~49 months for second course. All-cause mortality (ACM): Up to ~86 months for first and second course.
Adverse Event Reporting Description ACM includes all randomized participants. Safety includes all participants receiving ≥1 dose of study treatment. Per protocol, AEs were collected and reported by treatment intervention irrespective of indication. Per protocol, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment were excluded as AEs. Participants receiving a second course of pembrolizumab per protocol were monitored for ACM and safety separately.
 
Arm/Group Title First Course Pembrolizumab 10 mg/kg Second Course Pembrolizumab 10 mg/kg
Hide Arm/Group Description Participants received pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years. Qualified participants who completed the first course of pembrolizumab 10 mg/kg IV over 30 minutes once every 2 weeks (Q2W) for up to ~2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 10 mg/kg IV Q2W for up to ~1 year.
All-Cause Mortality
First Course Pembrolizumab 10 mg/kg Second Course Pembrolizumab 10 mg/kg
Affected / at Risk (%) Affected / at Risk (%)
Total   426/477 (89.31%)      6/11 (54.55%)    
Hide Serious Adverse Events
First Course Pembrolizumab 10 mg/kg Second Course Pembrolizumab 10 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   160/475 (33.68%)      3/11 (27.27%)    
Blood and lymphatic system disorders     
Anaemia † 1  5/475 (1.05%)  5 0/11 (0.00%)  0
Autoimmune haemolytic anaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Thrombocytopenia † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Atrial fibrillation † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Atrial tachycardia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Atrioventricular block complete † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Myocardial infarction † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pericardial effusion † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pulseless electrical activity † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Ear and labyrinth disorders     
Ear haemorrhage † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Endocrine disorders     
Hypercalcaemia of malignancy † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Hypothyroidism † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain † 1  4/475 (0.84%)  4 0/11 (0.00%)  0
Abdominal pain upper † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Ascites † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Colitis † 1  7/475 (1.47%)  8 0/11 (0.00%)  0
Constipation † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Diarrhoea † 1  5/475 (1.05%)  5 0/11 (0.00%)  0
Enteritis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Enterocolitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Gastritis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Gastrointestinal haemorrhage † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Gastrointestinal ulcer † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Haemorrhoids † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Ileus † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Intestinal ischaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Intestinal obstruction † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Large intestinal haemorrhage † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Malignant gastrointestinal obstruction † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Melaena † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pancreatitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Small intestinal obstruction † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Subileus † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Upper gastrointestinal haemorrhage † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Vomiting † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
General disorders     
Chest pain † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Complication associated with device † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Death † 1  4/475 (0.84%)  4 0/11 (0.00%)  0
General physical health deterioration † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Influenza like illness † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Malaise † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Non-cardiac chest pain † 1  1/475 (0.21%)  2 0/11 (0.00%)  0
Oedema † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pyrexia † 1  8/475 (1.68%)  11 0/11 (0.00%)  0
Hepatobiliary disorders     
Acute hepatic failure † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Autoimmune hepatitis † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Biliary colic † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Biliary obstruction † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Cholangitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Cholestasis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hepatic cytolysis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hepatic failure † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hepatitis † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Hyperbilirubinaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Jaundice † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Liver disorder † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Immune system disorders     
Cytokine release syndrome † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Infections and infestations     
Abdominal sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Bacteraemia † 1  3/475 (0.63%)  4 0/11 (0.00%)  0
Biliary sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Cellulitis † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Clostridium difficile colitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Device related bacteraemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Device related infection † 1  1/475 (0.21%)  2 0/11 (0.00%)  0
Device related sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Escherichia sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Gastroenteritis viral † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Helicobacter infection † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Infection † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Infectious mononucleosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Infectious pleural effusion † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Liver abscess † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Lower respiratory tract infection † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Lower respiratory tract infection bacterial † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Meningitis bacterial † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Oropharyngeal candidiasis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Osteomyelitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Otitis media † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pelvic abscess † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Peritonitis † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Pneumonia † 1  6/475 (1.26%)  6 0/11 (0.00%)  0
Pulmonary sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Salmonellosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Sepsis † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Septic shock † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Streptococcal sepsis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Subcutaneous abscess † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Urinary tract infection † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Wound infection † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Injury, poisoning and procedural complications     
Femoral neck fracture † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Gastroenteritis radiation † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Post procedural complication † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Investigations     
Alanine aminotransferase increased † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Aspartate aminotransferase increased † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Blood creatine phosphokinase increased † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Transaminases increased † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Metabolism and nutrition disorders     
Decreased appetite † 1  5/475 (1.05%)  5 0/11 (0.00%)  0
Food intolerance † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hypercalcaemia † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Hypoglycaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hypokalaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hyponatraemia † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Hypovolaemia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Type 2 diabetes mellitus † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Arthritis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Back pain † 1  2/475 (0.42%)  2 1/11 (9.09%)  1
Flank pain † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Joint effusion † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pain in extremity † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Rhabdomyolysis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain † 1  5/475 (1.05%)  5 0/11 (0.00%)  0
Malignant melanoma † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Myelodysplastic syndrome † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Squamous cell carcinoma of skin † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Tumour associated fever † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Tumour compression † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Tumour pain † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Nervous system disorders     
Altered state of consciousness † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Epilepsy † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Guillain-Barre syndrome † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hydrocephalus † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Ischaemic stroke † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Migraine † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Myelitis transverse † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Neuropathy peripheral † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Presyncope † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Seizure † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Syncope † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Product Issues     
Device occlusion † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Psychiatric disorders     
Anxiety † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Confusional state † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Depression † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Mental status changes † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury † 1  2/475 (0.42%)  2 1/11 (9.09%)  1
Haematuria † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hydronephrosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Renal failure † 1  2/475 (0.42%)  2 1/11 (9.09%)  1
Ureteric dilatation † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Urinary retention † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Reproductive system and breast disorders     
Intermenstrual bleeding † 1  1/475 (0.21%)  3 0/11 (0.00%)  0
Vaginal haemorrhage † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Vulvovaginal pain † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1  3/475 (0.63%)  3 0/11 (0.00%)  0
Haemoptysis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Interstitial lung disease † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Noninfective bronchitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pleural effusion † 1  8/475 (1.68%)  9 0/11 (0.00%)  0
Pneumonia aspiration † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pneumonitis † 1  5/475 (1.05%)  5 0/11 (0.00%)  0
Pneumothorax † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Pulmonary embolism † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Respiratory distress † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Tracheal stenosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Dermatitis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Pemphigoid † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Rash † 1  2/475 (0.42%)  2 0/11 (0.00%)  0
Vascular disorders     
Haemorrhage † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Hypotension † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Lymphoedema † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Lymphorrhoea † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
Orthostatic hypotension † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Thrombosis † 1  1/475 (0.21%)  1 0/11 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
First Course Pembrolizumab 10 mg/kg Second Course Pembrolizumab 10 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   429/475 (90.32%)      10/11 (90.91%)    
Blood and lymphatic system disorders     
Anaemia † 1  87/475 (18.32%)  101 0/11 (0.00%)  0
Iron deficiency anaemia † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Ear and labyrinth disorders     
Hypoacusis † 1  2/475 (0.42%)  2 1/11 (9.09%)  1
Endocrine disorders     
Hypothyroidism † 1  38/475 (8.00%)  39 0/11 (0.00%)  0
Eye disorders     
Cataract † 1  5/475 (1.05%)  5 1/11 (9.09%)  1
Dry eye † 1  11/475 (2.32%)  11 2/11 (18.18%)  2
Uveitis † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Gastrointestinal disorders     
Abdominal pain † 1  54/475 (11.37%)  59 0/11 (0.00%)  0
Abdominal pain upper † 1  28/475 (5.89%)  31 1/11 (9.09%)  1
Constipation † 1  93/475 (19.58%)  105 1/11 (9.09%)  1
Diarrhoea † 1  102/475 (21.47%)  177 3/11 (27.27%)  3
Dry mouth † 1  29/475 (6.11%)  30 1/11 (9.09%)  1
Nausea † 1  124/475 (26.11%)  149 0/11 (0.00%)  0
Vomiting † 1  75/475 (15.79%)  99 1/11 (9.09%)  1
Oral pain † 1  8/475 (1.68%)  9 1/11 (9.09%)  1
Abdominal pain lower † 1  7/475 (1.47%)  7 1/11 (9.09%)  1
Stomatitis † 1  14/475 (2.95%)  19 2/11 (18.18%)  2
General disorders     
Asthenia † 1  59/475 (12.42%)  68 1/11 (9.09%)  1
Fatigue † 1  165/475 (34.74%)  176 0/11 (0.00%)  0
Oedema peripheral † 1  43/475 (9.05%)  47 1/11 (9.09%)  1
Pyrexia † 1  74/475 (15.58%)  97 0/11 (0.00%)  0
Chest pain † 1  20/475 (4.21%)  23 1/11 (9.09%)  1
Influenza like illness † 1  11/475 (2.32%)  16 2/11 (18.18%)  3
Infections and infestations     
Conjunctivitis † 1  7/475 (1.47%)  7 2/11 (18.18%)  2
Gingivitis † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Lower respiratory tract infection † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Oral candidiasis † 1  7/475 (1.47%)  7 1/11 (9.09%)  1
Upper respiratory tract infection † 1  21/475 (4.42%)  27 1/11 (9.09%)  1
Mucosal infection † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Viral upper respiratory tract infection † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Injury, poisoning and procedural complications     
Lumbar vertebral fracture † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Contusion † 1  4/475 (0.84%)  4 1/11 (9.09%)  1
Investigations     
Alanine aminotransferase increased † 1  31/475 (6.53%)  39 1/11 (9.09%)  1
Aspartate aminotransferase increased † 1  37/475 (7.79%)  45 1/11 (9.09%)  1
Blood alkaline phosphatase increased † 1  40/475 (8.42%)  41 0/11 (0.00%)  0
Weight decreased † 1  35/475 (7.37%)  36 0/11 (0.00%)  0
Blood lactate dehydrogenase increased † 1  4/475 (0.84%)  7 1/11 (9.09%)  1
Hepatic enzyme increased † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Metabolism and nutrition disorders     
Decreased appetite † 1  102/475 (21.47%)  106 0/11 (0.00%)  0
Hypoalbuminaemia † 1  35/475 (7.37%)  37 0/11 (0.00%)  0
Hypokalaemia † 1  31/475 (6.53%)  33 0/11 (0.00%)  0
Hypomagnesaemia † 1  37/475 (7.79%)  46 0/11 (0.00%)  0
Hyponatraemia † 1  34/475 (7.16%)  36 1/11 (9.09%)  1
Hypocalcaemia † 1  13/475 (2.74%)  13 1/11 (9.09%)  1
Hypoglycaemia † 1  3/475 (0.63%)  3 1/11 (9.09%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  77/475 (16.21%)  101 2/11 (18.18%)  2
Back pain † 1  56/475 (11.79%)  64 3/11 (27.27%)  4
Myalgia † 1  38/475 (8.00%)  49 0/11 (0.00%)  0
Pain in extremity † 1  30/475 (6.32%)  34 0/11 (0.00%)  0
Arthritis † 1  5/475 (1.05%)  6 1/11 (9.09%)  1
Musculoskeletal chest pain † 1  18/475 (3.79%)  18 1/11 (9.09%)  1
Nervous system disorders     
Dizziness † 1  42/475 (8.84%)  54 0/11 (0.00%)  0
Headache † 1  63/475 (13.26%)  73 1/11 (9.09%)  1
Memory impairment † 1  3/475 (0.63%)  3 1/11 (9.09%)  1
Psychiatric disorders     
Depression † 1  25/475 (5.26%)  26 0/11 (0.00%)  0
Insomnia † 1  44/475 (9.26%)  45 0/11 (0.00%)  0
Renal and urinary disorders     
Hematuria † 1  10/475 (2.11%)  19 1/11 (9.09%)  1
Reproductive system and breast disorders     
Vulvovaginal dryness † 1  1/475 (0.21%)  1 1/11 (9.09%)  1
Respiratory, thoracic and mediastinal disorders     
Cough † 1  69/475 (14.53%)  89 0/11 (0.00%)  0
Dyspnoea † 1  60/475 (12.63%)  67 0/11 (0.00%)  0
Dysphonia † 1  16/475 (3.37%)  17 1/11 (9.09%)  1
Pneumonitis † 1  8/475 (1.68%)  8 1/11 (9.09%)  1
Skin and subcutaneous tissue disorders     
Dry skin † 1  24/475 (5.05%)  25 2/11 (18.18%)  2
Pruritus † 1  69/475 (14.53%)  88 2/11 (18.18%)  2
Rash † 1  56/475 (11.79%)  71 1/11 (9.09%)  1
Rash maculo-papular † 1  25/475 (5.26%)  28 0/11 (0.00%)  0
Dermatitis acneiform † 1  3/475 (0.63%)  3 1/11 (9.09%)  1
Palmar-plantar erythrodysaesthesia syndrome † 1  2/475 (0.42%)  2 1/11 (9.09%)  1
Rash pruritic † 1  3/11 (27.27%)  5 1/11 (9.09%)  1
Intertrigo † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Skin discolouration † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
Vascular disorders     
Hypotension † 1  20/475 (4.21%)  21 1/11 (9.09%)  1
Jugular vein thrombosis † 1  0/475 (0.00%)  0 1/11 (9.09%)  1
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Publications of Results:
Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):623-630. doi: 10.1016/S1470-2045(17)30169-9. Epub 2017 Mar 11.
Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. doi: 10.1093/annonc/mdx029.
Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.
Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Epub 2017 Aug 16.
Doi T, Piha-Paul SA, Jalal SI, Saraf S, Lunceford J, Koshiji M, Bennouna J. Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma. J Clin Oncol. 2018 Jan 1;36(1):61-67. doi: 10.1200/JCO.2017.74.9846. Epub 2017 Nov 8.
Frenel JS, Le Tourneau C, O'Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van Brummelen EMJ, Rugo HS, Thomas S, Saraf S, Rangwala R, Varga A. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol. 2017 Dec 20;35(36):4035-4041. doi: 10.1200/JCO.2017.74.5471. Epub 2017 Nov 2.
O'Neil BH, Wallmark JM, Lorente D, Elez E, Raimbourg J, Gomez-Roca C, Ejadi S, Piha-Paul SA, Stein MN, Abdul Razak AR, Dotti K, Santoro A, Cohen RB, Gould M, Saraf S, Stein K, Han SW. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PLoS One. 2017 Dec 28;12(12):e0189848. doi: 10.1371/journal.pone.0189848. eCollection 2017.
Cohen RB, Delord JP, Doi T, Piha-Paul SA, Liu SV, Gilbert J, Algazi AP, Damian S, Hong RL, Le Tourneau C, Day D, Varga A, Elez E, Wallmark J, Saraf S, Thanigaimani P, Cheng J, Keam B. Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. Am J Clin Oncol. 2018 Nov;41(11):1083-1088. doi: 10.1097/COC.0000000000000429.
Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, Sachdev J, Le Tourneau C, van Brummelen EMJ, Varga A, Salgado R, Loi S, Saraf S, Pietrangelo D, Karantza V, Tan AR. Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Clin Cancer Res. 2018 Jun 15;24(12):2804-2811. doi: 10.1158/1078-0432.CCR-17-3452. Epub 2018 Mar 20.
Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC. Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541. doi: 10.1200/JCO.2017.72.5952. Epub 2017 May 10.
Varga A, Piha-Paul S, Ott PA, Mehnert JM, Berton-Rigaud D, Morosky A, Yang P, Ruman J, Matei D. Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Gynecol Oncol. 2019 Feb;152(2):243-250. doi: 10.1016/j.ygyno.2018.11.017. Epub 2018 Dec 3.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT02054806    
Other Study ID Numbers: 3475-028
142515 ( Registry Identifier: JAPIC-CTI )
MK-3475-028 ( Other Identifier: Merck )
KEYNOTE-28 ( Other Identifier: Merck )
2013-004507-39 ( EudraCT Number )
First Submitted: February 3, 2014
First Posted: February 4, 2014
Results First Submitted: April 19, 2022
Results First Posted: October 30, 2023
Last Update Posted: October 30, 2023