ClinicalTrials.gov
History of Changes for Study: NCT03635567
Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)
Latest version (submitted January 12, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 15, 2018 None (earliest Version on record)
2 August 28, 2018 Oversight and Study Status
3 September 14, 2018 Study Status
4 October 24, 2018 Recruitment Status, Study Status and Contacts/Locations
5 November 11, 2018 Study Status
6 November 14, 2018 Study Status and Contacts/Locations
7 November 22, 2018 Contacts/Locations and Study Status
8 November 29, 2018 Contacts/Locations and Study Status
9 December 6, 2018 Study Status, IPDSharing and Contacts/Locations
10 December 13, 2018 Contacts/Locations and Study Status
11 December 21, 2018 Contacts/Locations and Study Status
12 December 27, 2018 Contacts/Locations and Study Status
13 January 4, 2019 Study Status and Contacts/Locations
14 January 18, 2019 Contacts/Locations and Study Status
15 January 25, 2019 Contacts/Locations and Study Status
16 January 31, 2019 Contacts/Locations and Study Status
17 February 8, 2019 Contacts/Locations and Study Status
18 February 14, 2019 Contacts/Locations and Study Status
19 February 22, 2019 Contacts/Locations and Study Status
20 March 1, 2019 Contacts/Locations and Study Status
21 March 8, 2019 Contacts/Locations and Study Status
22 March 14, 2019 Contacts/Locations and Study Status
23 March 22, 2019 Contacts/Locations and Study Status
24 March 26, 2019 Contacts/Locations and Study Status
25 April 5, 2019 Contacts/Locations and Study Status
26 April 11, 2019 Contacts/Locations and Study Status
27 April 17, 2019 Contacts/Locations and Study Status
28 April 26, 2019 Contacts/Locations and Study Status
29 May 3, 2019 Contacts/Locations and Study Status
30 May 9, 2019 Contacts/Locations and Study Status
31 May 17, 2019 Contacts/Locations and Study Status
32 May 30, 2019 Contacts/Locations and Study Status
33 June 7, 2019 Study Status
34 June 13, 2019 Contacts/Locations and Study Status
35 July 8, 2019 Study Status, Study Identification and Eligibility
36 July 25, 2019 Contacts/Locations and Study Status
37 August 8, 2019 Contacts/Locations and Study Status
38 August 21, 2019 Contacts/Locations, Study Status and Study Identification
39 August 29, 2019 Contacts/Locations and Study Status
40 September 4, 2019 Study Status and Contacts/Locations
41 September 13, 2019 Contacts/Locations and Study Status
42 October 16, 2019 Contacts/Locations and Study Status
43 December 12, 2019 Contacts/Locations and Study Status
44 January 10, 2020 Recruitment Status, Study Status, Contacts/Locations and References
45 November 11, 2020 Outcome Measures, Study Status, Conditions and Study Description
46 June 16, 2022 Study Status
47 September 2, 2022 Study Status
48 October 19, 2022 Study Status and Study Design
49 September 20, 2023 Outcome Measures, Study Status, References, Document Section, Results, Eligibility and Arms and Interventions
50 October 28, 2023 Outcome Measures and Study Status
51 January 12, 2024 Study Status and References
Comparison Format:
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Study NCT03635567
Submitted Date:  October 28, 2023 (v50)
Open or close this module Study Identification
Unique Protocol ID: 3475-826
Brief Title: Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)
Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (KEYNOTE-826)
Secondary IDs: MK-3475-826 [Merck]
KEYNOTE-826 [Merck]
184183 [Registry Identifier: JAPAC-CTI]
2018-001440-53 [EudraCT Number]
Open or close this module Study Status
Record Verification: October 2023
Overall Status: Active, not recruiting
Study Start: October 25, 2018
Primary Completion: October 3, 2022 [Actual]
Study Completion: June 4, 2024 [Anticipated]
First Submitted: August 15, 2018
First Submitted that
Met QC Criteria:		 August 15, 2018
First Posted: August 17, 2018 [Actual]
Results First Submitted: September 20, 2023
Results First Submitted that
Met QC Criteria:		 September 20, 2023
Results First Posted: October 12, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:		 October 28, 2023
Last Update Posted: November 14, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) plus one of four platinum-based chemotherapy regimens compared to the efficacy and safety of placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include: paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab.

The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the Investigator, or, 2) Overall Survival (OS).
Detailed Description:
Open or close this module Conditions
Conditions: Cervical Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 617 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab+Chemotherapy
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.
 Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Paclitaxel
IV infusion
Other Names:
  • TAXOL®
Drug: Cisplatin
IV infusion
Other Names:
  • PLATINOL®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: Bevacizumab
IV infusion
Other Names:
  • AVASTIN®
Placebo Comparator: Placebo+Chemotherapy
On Day 1 of each 21-day cycle, participants receive an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.
 Drug: Paclitaxel
IV infusion
Other Names:
  • TAXOL®
Drug: Cisplatin
IV infusion
Other Names:
  • PLATINOL®
Drug: Carboplatin
IV infusion
Other Names:
  • PARAPLATIN®
Biological: Bevacizumab
IV infusion
Other Names:
  • AVASTIN®
Drug: Placebo to pembrolizumab
IV infusion
Other Names:
  • Normal Saline or Dextrose solution
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
[ Time Frame: Up to approximately 46 months ]

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥1 is presented.
2. PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
[ Time Frame: Up to approximately 46 months ]

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented.
3. PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10
[ Time Frame: Up to approximately 46 months ]

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥10 is presented.
4. Overall Survival (OS) in Participants With PD-L1 CPS ≥1
[ Time Frame: Up to approximately 46 months ]

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥1 is presented.
5. OS in All Participants
[ Time Frame: Up to approximately 46 months ]

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.
6. OS in Participants With PD-L1 CPS ≥10
[ Time Frame: Up to approximately 46 months ]

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥10 is presented.
Secondary Outcome Measures:
1. Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
[ Time Frame: Up to approximately 46 months ]

ORR was defined as the percentage of the participants in the analysis population who have 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, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator is presented.
2. Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
[ Time Frame: Up to approximately 46 months ]

For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented.
3. Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
[ Time Frame: 12 months ]

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS Rate was defined as the percentage of participants that were PFS event-free at Month 12. The PFS Rate per RECIST 1.1 as assessed by Investigator at Month 12 is presented.
4. PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
[ Time Frame: Up to approximately 46 months ]

PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR is presented.
5. Number of Participants Who Experienced an Adverse Event (AE)
[ Time Frame: Up to approximately 46 months ]

An AE was 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. The number of participants who experienced an AE is presented.
6. Number of Participants Who Experienced a Serious AE (SAE)
[ Time Frame: Up to approximately 46 months ]

An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented.
7. Number of Participants Who Experienced an Immune-related AE (irAE)
[ Time Frame: Up to approximately 46 months ]

AEs associated with pembrolizumab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. For this study irAEs included, but were not limited to: -Pneumonitis;

  • Diarrhea/Colitis;
  • Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin;
  • Type 1 diabetes mellitus or Hyperglycemia;
  • Hypophysitis;
  • Hyperthyroidism;
  • Hypothyroidism;
  • Nephritis and Renal dysfunction; and
  • Myocarditis. The number of participants who experienced an irAE is presented.
8. Number of Participants Who Discontinued Study Treatment Due to an AE
[ Time Frame: Up to approximately 43 months ]

The number of participants who discontinued study treatment due to an AE is presented.
9. Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
[ Time Frame: Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months ]

The EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. Participant responses to "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Raw scores are standardized with linear transformation so that scores range from 0-100. A higher combined score indicates a better overall health status. Participant post-baseline scores were classified based on change from baseline, "Improved": a ≥10-point improvement in score and confirmed by the next visit; "Stable": a ≥10-point increase or <10-point change in score OR a <10-point change in score and a ≥10-point increase in score at the next visit; or "Deteriorated": a ≥10-point deterioration in score when the criteria for improvement/stability weren't met. Participants who didn't meet "Improved", "Stable", or "Deteriorated" criteria reported as "Other".
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Has persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation). Prior chemotherapy utilized as a radiosensitizing agent and completed at least 2 weeks prior to randomization with resolution of all treatment-related toxicities is allowed. AEs due to previous treatments should be resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are eligible.
  • Not pregnant or breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP), b.) A WOCBP must agree to use effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab/placebo and 210 days after the last dose of chemotherapy/bevacizumab
  • Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
  • Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to randomization
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to randomization
  • Has adequate organ function

Exclusion Criteria:

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast cancer) that have undergone potentially curative therapy are not excluded.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137)
  • Has received prior systemic chemotherapy for treatment of cervical cancer.
  • Has not recovered adequately from toxicity and/or complications from major surgery prior to randomization
  • Has received prior radiotherapy within 2 weeks prior to randomization. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Has received a live vaccine within 30 days prior to randomization
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
  • Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days following last dose of pembrolizumab/placebo and 210 days following last dose of chemotherapy/bevacizumab
  • Has had an allogeneic tissue/solid organ transplant
Open or close this module Contacts/Locations
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations: United States, Alaska
Alaska Women's Cancer Care ( Site 1770)
Anchorage, Alaska, United States, 99508
United States, Arizona
Arizona Oncology Associates, PC- HAL ( Site 8005)
Phoenix, Arizona, United States, 85016
United States, California
UC Irvine Health ( Site 1796)
Orange, California, United States, 92868
United States, Connecticut
Smilow Cancer Hospital at Yale New Haven ( Site 1809)
New Haven, Connecticut, United States, 06510
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute ( Site 1754)
Tampa, Florida, United States, 33612
United States, Georgia
Georgia Cancer Center at Augusta University ( Site 1767)
Augusta, Georgia, United States, 30912
United States, Michigan
Barbara Ann Karmanos Cancer Institute ( Site 1785)
Detroit, Michigan, United States, 48201
Henry Ford Health System ( Site 1810)
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School of Medicine ( Site 1779)
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at University Hospital ( Site 1762)
Newark, New Jersey, United States, 07103
Holy Name Medical Center ( Site 1776)
Teaneck, New Jersey, United States, 07666
United States, New York
Mount Sinai Chelsea ( Site 1760)
New York, New York, United States, 10011
Columbia University Medical Center ( Site 1800)
New York, New York, United States, 10032
United States, Ohio
OSU Wexner Medical Center ( Site 1817)
Hilliard, Ohio, United States, 43026
United States, Oklahoma
University of Oklahoma- Stephenson Oklahoma Cancer Center ( Site 1784)
Oklahoma City, Oklahoma, United States, 73104
Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1768)
Tulsa, Oklahoma, United States, 74146
United States, South Carolina
MUSC Hollings Cancer Center ( Site 1819)
Charleston, South Carolina, United States, 29425
United States, Tennessee
West Cancer Center - East Campus ( Site 1763)
Germantown, Tennessee, United States, 38138
United States, Texas
Texas Oncology-San Antonio Medical Center ( Site 8001)
San Antonio, Texas, United States, 78240
United States, Washington
Seattle Cancer Care Alliance ( Site 1777)
Seattle, Washington, United States, 98109
Argentina
Hospital Aleman ( Site 1005)
Buenos Aires, Argentina, C1118AAT
Hospital de Oncologia Angel Roffo ( Site 1003)
Buenos Aires, Argentina, C1417DTB
Instituto Medico Especializado Alexander Fleming ( Site 1009)
Buenos Aires, Argentina, C1426ANZ
Centro Oncologico Riojano Integral ( Site 1004)
La Rioja, Argentina, F5300COE
Centro Medico San Roque ( Site 1001)
Tucuman, Argentina, T4000IAK
Argentina, Buenos Aires
Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1006)
Berazategui, Buenos Aires, Argentina, B1884BBF
Australia
Monash Health-Monash Medical Centre ( Site 1519)
Clayton, Australia, 3168
Australia, New South Wales
Royal North Shore Hospital ( Site 1514)
St Leonards, New South Wales, Australia, 2065
Australia, Queensland
Mater Misericordiae Ltd Mater Cancer Care Centre ( Site 1521)
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Flinders Medical Centre ( Site 1513)
Bedford Park, South Australia, Australia, 5042
Australia, Western Australia
St John of God Subiaco Hospital ( Site 1512)
Subiaco, Western Australia, Australia, 6008
Canada
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 1724)
Quebec, Canada, G1R 2J6
Canada, Alberta
Tom Baker Cancer Centre ( Site 1728)
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 1734)
Kelowna, British Columbia, Canada, V1Y 5L3
BC Cancer - Vancouver Center ( Site 1722)
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba ( Site 1725)
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre ( Site 1731)
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Juravinski Cancer Centre ( Site 1735)
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program - London HSC ( Site 1723)
London, Ontario, Canada, N6A 5W9
The Ottawa Hospital Cancer Centre ( Site 1736)
Ottawa, Ontario, Canada, K1H 8L6
Sunnybrook Research Institute ( Site 1733)
Toronto, Ontario, Canada, M4N 3M5
Princess Margaret Cancer Centre ( Site 1732)
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CIUSSS du Saguenay-Lac-St-Jean ( Site 1729)
Chicoutimi, Quebec, Canada, G7H 5H6
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 1726)
Montreal, Quebec, Canada, H1T 2M4
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 1721)
Montreal, Quebec, Canada, H2X 3E4
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 1730)
Sherbrooke, Quebec, Canada, J1H 5N4
Chile
Fundacion Arturo Lopez Perez FALP ( Site 1061)
Santiago, Chile, 7500921
Sociedad Oncovida S.A. ( Site 1069)
Santiago, Chile, 7510032
Centro de Cancer Nuestra Senora de la Esperanza ( Site 1063)
Santiago, Chile, 8330024
Instituto Clinico Oncologico del Sur ( Site 1062)
Temuco, Chile, 4810469
Chile, Valparaiso
Oncocentro ( Site 1065)
Vina del Mar, Valparaiso, Chile, 2520598
Colombia
Biomelab S A S ( Site 1104)
Barranquilla, Colombia, 080002
Oncomedica S.A. ( Site 1098)
Monteria, Colombia, 230002
Instituto Cancerologico de Narino Ltda ( Site 1097)
Pasto, Colombia, 520001
Colombia, Cesar
Sociedad de Oncologia y Hematologia del Cesar Ltda. ( Site 1103)
Valledupar, Cesar, Colombia, 200001
Colombia, Cundinamarca
Instituto Nacional de Cancerologia E.S.E ( Site 1095)
Bogota, Cundinamarca, Colombia, 111511
Colombia, Valle
Hemato Oncologos S.A. ( Site 1100)
Cali, Valle, Colombia, 760046
France
Centre Jean Perrin ( Site 1181)
Clermont Ferrand, France, 63011
Institut Paoli Calmettes ( Site 1182)
Marseille, France, 13009
Groupe Hospitalier Broca Cochin Hotel Dieu ( Site 1183)
Paris, France, 75014
Centre Eugene Marquis ( Site 1187)
Rennes, France, 35042
Institut Curie - Centre Rene Huguenin ( Site 1185)
Saint-Cloud, France, 92210
Germany
Universitaetsklinikum Carl Gustav Carus ( Site 1211)
Dresden, Germany, 01307
Universitaetsklinikum Duesseldorf ( Site 1220)
Duesseldorf, Germany, 40225
Universitatsklinikum Essen AoR ( Site 1213)
Essen, Germany, 45147
Universitatsklinikum Hamburg-Eppendorf ( Site 1212)
Hamburg, Germany, 20251
Gynoncological Practice Lueck. Schrader. Noeding ( Site 1224)
Hannover, Germany, 30177
Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 1214)
Kiel, Germany, 24105
Rotkreuzklinikum Muenchen gGmbH. Studienzentrale Frauenklinik ( Site 1225)
Muenchen, Germany, 80637
Klinikum Oldenburg AoeR ( Site 1218)
Oldenburg, Germany, 26133
Universitaet Regensburg ( Site 1221)
Regensburg, Germany, 93053
Israel
Soroka Medical Center ( Site 1363)
Beer-Sheva, Israel, 8410101
Rambam Medical Center ( Site 1364)
Haifa, Israel, 3525408
Shaare Zedek Medical Center ( Site 1366)
Jerusalem, Israel, 9103102
Hadassah Medical Center. Ein Kerem ( Site 1367)
Jerusalem, Israel, 9112001
Rabin Medical Center ( Site 1365)
Petah Tikva, Israel, 4941492
Chaim Sheba Medical Center ( Site 1361)
Ramat Gan, Israel, 5265601
Sourasky Medical Center ( Site 1362)
Tel Aviv, Israel, 6423906
Italy
Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 1243)
Aviano, Italy, 33081
A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1245)
Bolgna, Italy, 40138
Istituto Nazionale Tumori ( Site 1251)
Milano, Italy, 20133
Istituto Europeo di Oncologia ( Site 1250)
Milano, Italy, 20141
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1242)
Napoli, Italy, 80131
Policlinico Universitario -Agostino Gemelli ( Site 1241)
Roma, Italy, 00168
Japan
National Cancer Center Hospital ( Site 1702)
Tokyo, Japan, 104-0045
The Jikei University Hospital ( Site 1697)
Tokyo, Japan, 105-8471
The Cancer Institute Hospital of JFCR ( Site 1698)
Tokyo, Japan, 135-8550
Keio University Hospital ( Site 1699)
Tokyo, Japan, 160-8582
Japan, Chiba
The Jikei University Kashiwa Hospital ( Site 1701)
Kashiwa, Chiba, Japan, 277-8567
National Cancer Center Hospital East ( Site 1704)
Kashiwa, Chiba, Japan, 277-8577
Japan, Ehime
Ehime University Hospital ( Site 1693)
Toon, Ehime, Japan, 791-0295
Japan, Fukuoka
Kurume University Hospital ( Site 1692)
Kurume, Fukuoka, Japan, 830-0011
Japan, Hokkaido
National Hospital Organization Hokkaido Cancer Center ( Site 1700)
Sapporo, Hokkaido, Japan, 003-0804
Japan, Hyogo
Hyogo Cancer Center ( Site 1705)
Akashi, Hyogo, Japan, 673-8558
Japan, Iwate
Iwate Medical University Hospital ( Site 1695)
Shiwa-gun, Iwate, Japan, 028-3695
Japan, Okinawa
University of the Ryukyus Hospital ( Site 1706)
Nakagami-gun, Okinawa, Japan, 903-0215
Japan, Saitama
Saitama Medical University International Medical Center ( Site 1691)
Hidaka, Saitama, Japan, 350-1298
Japan, Shizuoka
Shizuoka Cancer Center Hospital and Research Institute ( Site 1703)
Sunto-gun, Shizuoka, Japan, 411-8777
Korea, Republic of
Keimyung University Dongsan Medical Center ( Site 1603)
Daegu, Korea, Republic of, 42601
Seoul National University Hospital ( Site 1602)
Seoul, Korea, Republic of, 03080
Asan Medical Center ( Site 1601)
Seoul, Korea, Republic of, 05505
Samsung Medical Center ( Site 1604)
Seoul, Korea, Republic of, 06351
Mexico
Centro Estatal de Cancerologia de Chihuahua ( Site 1123)
Chihuahua, Mexico, 31000
Consultorio de Medicina Especializada del Sector Privado ( Site 1129)
Ciudad de Mexico, Mexico, 03100
CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 1127)
Ciudad de Mexico, Mexico, 06100
Instituto Nacional de Cancerologia. ( Site 1130)
Mexico, Mexico, 14080
Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 1125)
San Pedro Garza Garcia, Mexico, 66269
Faicic S de RL de CV ( Site 1133)
Veracruz, Mexico, 91900
Mexico, Yucatan
Medical Care and Research S.A. de C.V. ( Site 1135)
Merida, Yucatan, Mexico, 97070
Peru
Centro Medico Monte Carmelo ( Site 1156)
Arequipa, Peru, 04001
Hospital Nacional Guillermo Almenara Irigoyen ( Site 1158)
Lima, Peru, 15033
Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 1157)
Lima, Peru, 15036
Instituto Nacional de Enfermedades Neoplasicas ( Site 1153)
Lima, Peru, 15038
Hospital Nacional Arzobispo Loayza ( Site 1159)
Lima, Peru, 15082
Hospital Nacional Maria Auxiliadora ( Site 1155)
Lima, Peru, 15801
Peru, La Libertad
Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 1152)
Trujillo, La Libertad, Peru, 13006
Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1331)
Kazan, Russian Federation, 420029
FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1334)
Moscow, Russian Federation, 115478
Medical Rehabilitation Center ( Site 1337)
Moscow, Russian Federation, 125367
Novosibirsk Regional Clinical Oncology Dispensary ( Site 1358)
Novosibirsk, Russian Federation, 630108
Municipal Clinical Oncology Center ( Site 1346)
Saint Petersburg, Russian Federation, 198255
National Research Ogarev Mordovia State University ( Site 1347)
Saransk, Russian Federation, 430005
National Medical Research Center of Oncology n.a. N. N. Petrov ( Site 1348)
St. Petersburg, Russian Federation, 197758
Tomsk Scientific Research Institute of Oncology ( Site 1360)
Tomsk, Russian Federation, 634028
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1345)
Ufa, Russian Federation, 450054
Spain
Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1276)
Badalona, Spain, 08916
MD Anderson Cancer Center Madrid ( Site 1273)
Madrid, Spain, 28033
Hospital Universitario Virgen Macarena ( Site 1274)
Sevilla, Spain, 41009
Spain, Guipuzcoa
Onkologikoa - Instituto Oncologico de San Sebastian ( Site 1275)
Doniostia - San Sebastian, Guipuzcoa, Spain, 20014
Spain, Madrid
Hospital Quiron Madrid ( Site 1277)
Pozuelo de Alarcon, Madrid, Spain, 28223
Taiwan
Kaohsiung Veterans General Hospital ( Site 1632)
Kaohsiung, Taiwan, 813
China Medical University Hospital ( Site 1635)
Taichung, Taiwan, 40447
Taichung Veterans General Hospital ( Site 1634)
Taichung, Taiwan, 40705
Koo Foundation Sun Yat-Sen Cancer Center ( Site 1636)
Taipei, Taiwan, 112
Taipei Veterans General Hospital ( Site 1631)
Taipei, Taiwan, 112
Chang Gung Medical Foundation. Linkou ( Site 1633)
Taoyuan, Taiwan, 33305
Turkey
Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1457)
Adana, Turkey, 01250
Hacettepe University Medical Faculty ( Site 1459)
Ankara, Turkey, 06230
Baskent Universitesi Ankara Hastanesi ( Site 1451)
Ankara, Turkey, 06490
Akdeniz Universitesi Tip Fakultesi ( Site 1453)
Antalya, Turkey, 07059
Medeniyet University Goztepe Egitim ve Arastırma Hast. Merdivenkoy ( Site 1458)
Istanbul, Turkey, 34722
Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1456)
Izmir, Turkey, 35040
Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 1452)
Konya, Turkey, 42080
Ukraine
City Clinical Hosp.4 of DCC ( Site 1482)
Dnipropetrovsk, Ukraine, 49102
MI Precarpathian Clinical Oncology Center ( Site 1487)
Ivano-Frankivsk, Ukraine, 76018
Communal non profit enterprise Regional Clinical Oncology Center ( Site 1489)
Kharkiv, Ukraine, 61070
National Cancer Institute of the MoH of Ukraine ( Site 1484)
Kyiv, Ukraine, 03022
MI Odessa Regional Oncological Centre ( Site 1493)
Odesa, Ukraine, 65055
Medical Centre LLC Oncolife ( Site 1485)
Zaporizhzhya, Ukraine, 69104
Open or close this module IPDSharing
Plan to Share IPD: Yes
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Links: Description: Merck Clinical Trials Information
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: June 10, 2022
Uploaded: 09/20/2023 08:33
File Name: Prot_SAP_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy
Arm/Group Description On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Period Title: Overall Study
Started 308 309
Treated 307 309
Received Second Course of Pembrolizumab 8 0
Completed 0 0
Not Completed 308 309
Reason Not Completed
Lost to Follow-up 0 2
Withdrawal by Subject 9 10
Ongoing in Study 125 76
Death 174 221
Open or close this module Baseline Characteristics
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+ChemotherapyTotal
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.Total of all reporting groups
Overall Number of Baseline Participants 308 309 617
Baseline Analysis Population Description [Not Specified]
Age, Continuous
Mean (Standard Deviation)
Unit of measure: Years
Number Analyzed308 Participants309 Participants617 Participants
51.7(11.9)50.7(12.7)51.2(12.3)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
Female
308
100%
309
100%
617
100%
Male
0
0%
0
0%
0
0%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
Hispanic or Latino
109
35.39%
121
39.16%
230
37.28%
Not Hispanic or Latino
193
62.66%
184
59.55%
377
61.1%
Unknown or Not Reported
6
1.95%
4
1.29%
10
1.62%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
American Indian or Alaska Native
18
5.84%
21
6.8%
39
6.32%
Asian
65
21.1%
45
14.56%
110
17.83%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
4
1.3%
2
0.65%
6
0.97%
White
170
55.19%
190
61.49%
360
58.35%
More than one race
32
10.39%
34
11%
66
10.7%
Unknown or Not Reported
19
6.17%
17
5.5%
36
5.83%
Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) Status [1]
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
PD-L1 CPS<1
35
11.36%
34
11%
69
11.18%
1≤ PD-L1 CPS<10
115
37.34%
116
37.54%
231
37.44%
PD-L1 CPS≥10
158
51.3%
159
51.46%
317
51.38%
 
[1]Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue. Randomization of participants in the study were stratified by their PD-L1 CPS at baseline (PD-L1 CPS<1, 1≤ PD-L1 CPS<10, or PD-L1 CPS≥10).
Metastatic at Initial Diagnosis [1]
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
Yes
94
30.52%
96
31.07%
190
30.79%
No
214
69.48%
213
68.93%
427
69.21%
 
[1]Measure Description: Randomization of participants was stratified by whether they were metastatic at initial diagnosis (Yes or No). Metastatic was defined as Stage IV based on the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) (2009).
Investigator Choice to Use Bevacizumab [1]
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed308 Participants309 Participants617 Participants
Yes
196
63.64%
193
62.46%
389
63.05%
No
112
36.36%
116
37.54%
228
36.95%
 
[1]Measure Description: Randomization of participants was stratified by the Investigator's choice for the participant to receive bevacizumab (Yes or No).
Open or close this module Outcome Measures
1. Primary Outcome:
Title Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥1 is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed273 275
Median (95% Confidence Interval)
Unit of Measure: Months
10.5(9.7 to 12.3) 8.2(6.3 to 8.5)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (hazard ratio [HR]) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.58
Confidence Interval(2-sided) 95%
0.47 to 0.71
Estimation Comments[Not specified]
2. Primary Outcome:
Title PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed308 309
Median (95% Confidence Interval)
Unit of Measure: Months
10.4(9.1 to 12.2) 8.2(6.4 to 8.4)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.61
Confidence Interval(2-sided) 95%
0.50 to 0.74
Estimation Comments[Not specified]
3. Primary Outcome:
Title PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥10 is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed158 159
Median (95% Confidence Interval)
Unit of Measure: Months
10.4(8.9 to 15.1) 8.1(6.2 to 8.8)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.52
Confidence Interval(2-sided) 95%
0.40 to 0.68
Estimation Comments[Not specified]
4. Primary Outcome:
Title Overall Survival (OS) in Participants With PD-L1 CPS ≥1
Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥1 is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed273 275
Median (95% Confidence Interval)
Unit of Measure: Months
28.6(22.1 to 38.0) 16.5(14.5 to 20.0)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.60
Confidence Interval(2-sided) 95%
0.49 to 0.74
Estimation Comments[Not specified]
5. Primary Outcome:
Title OS in All Participants
Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed308 309
Median (95% Confidence Interval)
Unit of Measure: Months
26.4(21.3 to 32.5) 16.8(14.6 to 19.4)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value based on log-rank test provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.63
Confidence Interval(2-sided) 95%
0.52 to 0.77
Estimation Comments[Not specified]
6. Primary Outcome:
Title OS in Participants With PD-L1 CPS ≥10
Description OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥10 is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed158 159
Median (95% Confidence Interval)
Unit of Measure: Months
29.6(20.6 to NA) [1] 17.4(14.0 to 24.7)
[1]NA Explanation: NA = Upper limit not reached at time of data cut-off due to insufficient number of participants with an event.
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison.
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.58
Confidence Interval(2-sided) 95%
0.44 to 0.78
Estimation Comments[Not specified]
7. Secondary Outcome:
Title Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Description ORR was defined as the percentage of the participants in the analysis population who have 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, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed308 309
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
66.2(60.7 to 71.5) 51.5(45.7 to 57.2)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison was based on Miettinen & Nurminen method stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison
MethodMiettinen & Nurminen method
Comments[Not specified]
Method of EstimationEstimation ParameterDifference in Percentage
Estimated Value14.9
Confidence Interval(2-sided) 95%
7.4 to 22.3
Estimation Comments[Not specified]
8. Secondary Outcome:
Title Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
Description For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized who demonstrated CR or PR.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed204 159
Median (95% Confidence Interval)
Unit of Measure: Months
18.0(10.5 to 32.3) 10.4(8.3 to 13.3)
9. Secondary Outcome:
Title Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
Description PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS Rate was defined as the percentage of participants that were PFS event-free at Month 12. The PFS Rate per RECIST 1.1 as assessed by Investigator at Month 12 is presented.
Time Frame 12 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed308 309
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
44.7(38.9 to 50.4) 33.1(27.7 to 38.7)
10. Secondary Outcome:
Title PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
Description PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants based on the treatment group to which they were randomized.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed308 309
Median (95% Confidence Interval)
Unit of Measure: Months
12.3(10.3 to 17.9) 8.3(8.1 to 9.0)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab+Chemotherapy, Placebo+Chemotherapy
CommentsTreatment comparison (HR) was based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB) (yes or no), bevacizumab use (yes or no), and PD-L1 status (CPS<1, CPS 1 to <10, or CPS ≥10).
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.0001
CommentsNo formal hypothesis testing performed; nominal p-value provided for treatment comparison
MethodStratified Log-Rank
CommentsNominal p-value based on log-rank test stratified by metastatic at initial diagnosis (FIGO [2009] stage IVB), bevacizumab use, and PD-L1 status.
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.60
Confidence Interval(2-sided) 95%
0.49 to 0.74
Estimation Comments[Not specified]
11. Secondary Outcome:
Title Number of Participants Who Experienced an Adverse Event (AE)
Description An AE was 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. The number of participants who experienced an AE is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants who received at least one dose of study treatment.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed307 309
Measure Type: Number
Unit of Measure: Number of participants
305
99.3%
307
99.4%
12. Secondary Outcome:
Title Number of Participants Who Experienced a Serious AE (SAE)
Description An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants who received at least one dose of study treatment.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed307 309
Measure Type: Number
Unit of Measure: Number of Participants
157
51.1%
132
42.7%
13. Secondary Outcome:
Title Number of Participants Who Experienced an Immune-related AE (irAE)
Description

AEs associated with pembrolizumab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. For this study irAEs included, but were not limited to: -Pneumonitis;

  • Diarrhea/Colitis;
  • Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin;
  • Type 1 diabetes mellitus or Hyperglycemia;
  • Hypophysitis;
  • Hyperthyroidism;
  • Hypothyroidism;
  • Nephritis and Renal dysfunction; and
  • Myocarditis. The number of participants who experienced an irAE is presented.
Time Frame Up to approximately 46 months
Outcome Measure Data
Analysis Population Description
All randomized participants who received at least one dose of study treatment.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed307 309
Measure Type: Number
Unit of Measure: Number of Participants
106
34.5%
51
16.5%
14. Secondary Outcome:
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Description The number of participants who discontinued study treatment due to an AE is presented.
Time Frame Up to approximately 43 months
Outcome Measure Data
Analysis Population Description
All randomized participants who received at least one dose of study treatment.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed307 309
Measure Type: Number
Unit of Measure: Number of Participants
125
40.7%
91
29.4%
15. Secondary Outcome:
Title Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
Description The EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. Participant responses to "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Raw scores are standardized with linear transformation so that scores range from 0-100. A higher combined score indicates a better overall health status. Participant post-baseline scores were classified based on change from baseline, "Improved": a ≥10-point improvement in score and confirmed by the next visit; "Stable": a ≥10-point increase or <10-point change in score OR a <10-point change in score and a ≥10-point increase in score at the next visit; or "Deteriorated": a ≥10-point deterioration in score when the criteria for improvement/stability weren't met. Participants who didn't meet "Improved", "Stable", or "Deteriorated" criteria reported as "Other".
Time Frame Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months
Outcome Measure Data
Analysis Population Description
Per protocol, all randomized participants who received at least one dose of study treatment and completed at least one EORTC QLQ-C30 assessment were analyzed. Participants with no EORTC QLQ-C30 assessment were not included in the analysis.
 
Arm/Group TitlePembrolizumab+ChemotherapyPlacebo+Chemotherapy
Arm/Group DescriptionOn Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity.
Overall Number of Participants Analyzed279 282
Measure Type: Number
Unit of Measure: Number of Participants
Improved
122
43.7%
86
30.5%
Stable
106
38%
139
49.3%
Deteriorated
42
15.1%
48
17%
Other
9
3.2%
9
3.2%
Open or close this module Adverse Events
 
Time Frame Up to approximately 46 months
Adverse Event Reporting Description Serious and Other adverse events (AEs) included all participants who received ≥1 dose of study drug. All-Cause Mortality included all randomized participants. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs. Data are reported by treatment received.
 
Arm/Group Title Pembrolizumab+Chemotherapy Placebo+Chemotherapy Pembrolizumab (Second Course)
Arm/Group Description On Day 1 of each 21-day cycle, participants received an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. On Day 1 of each 21-day cycle, participants received an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments were administered until disease progression or toxicity. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 200 mg IV on Day 1 of each 21-day cycle.
All-Cause Mortality
  Pembrolizumab+ChemotherapyPlacebo+ChemotherapyPembrolizumab (Second Course)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 178 / 308 (57.79%)228 / 309 (73.79%)0 / 8 (0%)
Serious Adverse Events
  Pembrolizumab+ChemotherapyPlacebo+ChemotherapyPembrolizumab (Second Course)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 157 / 307 (51.14%)132 / 309 (42.72%)3 / 8 (37.5%)
Blood and lymphatic system disorders
Anaemia † A 14 / 307 (4.56%)1412 / 309 (3.88%)140 / 8 (0%)0
Bicytopenia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Febrile neutropenia † A 21 / 307 (6.84%)2513 / 309 (4.21%)140 / 8 (0%)0
Leukopenia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Lymphadenitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Neutropenia † A 4 / 307 (1.3%)53 / 309 (0.97%)30 / 8 (0%)0
Pancytopenia † A 2 / 307 (0.65%)23 / 309 (0.97%)30 / 8 (0%)0
Thrombocytopenia † A 3 / 307 (0.98%)32 / 309 (0.65%)30 / 8 (0%)0
Cardiac disorders
Acute myocardial infarction † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Atrial fibrillation † A 4 / 307 (1.3%)41 / 309 (0.32%)10 / 8 (0%)0
Bundle branch block † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Cardiac arrest † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Cardiac failure congestive † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Mitral valve stenosis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Myocardial infarction † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Myocarditis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Stress cardiomyopathy † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Supraventricular tachycardia † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Endocrine disorders
Adrenal insufficiency † A 3 / 307 (0.98%)30 / 309 (0%)00 / 8 (0%)0
Hyperthyroidism † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Hypophysitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Eye disorders
Optic neuropathy † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Gastrointestinal disorders
Abdominal pain † A 2 / 307 (0.65%)23 / 309 (0.97%)30 / 8 (0%)0
Abdominal pain lower † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Abdominal pain upper † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Anal fistula † A 1 / 307 (0.33%)20 / 309 (0%)00 / 8 (0%)0
Anal haemorrhage † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Anal ulcer † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Colitis † A 3 / 307 (0.98%)33 / 309 (0.97%)30 / 8 (0%)0
Constipation † A 0 / 307 (0%)02 / 309 (0.65%)20 / 8 (0%)0
Diarrhoea † A 5 / 307 (1.63%)52 / 309 (0.65%)20 / 8 (0%)0
Duodenal perforation † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Enterocolitis † A 1 / 307 (0.33%)20 / 309 (0%)00 / 8 (0%)0
Enterovesical fistula † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Gastric haemorrhage † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Gastric ulcer † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Gastritis † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Gingival bleeding † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Ileus † A 0 / 307 (0%)01 / 309 (0.32%)40 / 8 (0%)0
Immune-mediated enterocolitis † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Intestinal obstruction † A 3 / 307 (0.98%)32 / 309 (0.65%)20 / 8 (0%)0
Intestinal perforation † A 2 / 307 (0.65%)21 / 309 (0.32%)10 / 8 (0%)0
Intestinal pseudo-obstruction † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Large intestinal obstruction † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Large intestine perforation † A 0 / 307 (0%)02 / 309 (0.65%)20 / 8 (0%)0
Nausea † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Pancreatitis acute † A 2 / 307 (0.65%)21 / 309 (0.32%)10 / 8 (0%)0
Proctitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Rectal haemorrhage † A 3 / 307 (0.98%)31 / 309 (0.32%)10 / 8 (0%)0
Rectal perforation † A 2 / 307 (0.65%)21 / 309 (0.32%)10 / 8 (0%)0
Small intestinal obstruction † A 0 / 307 (0%)03 / 309 (0.97%)30 / 8 (0%)0
Small intestinal perforation † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Subileus † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Upper gastrointestinal haemorrhage † A 0 / 307 (0%)02 / 309 (0.65%)20 / 8 (0%)0
Volvulus † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Vomiting † A 3 / 307 (0.98%)32 / 309 (0.65%)20 / 8 (0%)0
General disorders
Asthenia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Chest pain † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Death † A 3 / 307 (0.98%)33 / 309 (0.97%)30 / 8 (0%)0
Fatigue † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
General physical health deterioration † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Infusion site extravasation † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Malaise † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Medical device site laceration † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Pseudocyst † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Pyrexia † A 9 / 307 (2.93%)95 / 309 (1.62%)50 / 8 (0%)0
Hepatobiliary disorders
Autoimmune hepatitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Biliary obstruction † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Cholecystitis acute † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Cholelithiasis † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Drug-induced liver injury † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Hepatobiliary disease † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Hepatotoxicity † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Immune-mediated cholangitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Immune-mediated hepatitis † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Immune system disorders
Anaphylactic reaction † A 1 / 307 (0.33%)20 / 309 (0%)00 / 8 (0%)0
Anaphylactic shock † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Contrast media allergy † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Drug hypersensitivity † A 0 / 307 (0%)03 / 309 (0.97%)30 / 8 (0%)0
Hypersensitivity † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
Infections and infestations
Abdominal sepsis † A 0 / 307 (0%)02 / 309 (0.65%)20 / 8 (0%)0
Abdominal wall abscess † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Abscess † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Acute hepatitis B † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Anal abscess † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Bacteraemia † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Bronchitis † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
COVID-19 † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
COVID-19 pneumonia † A 1 / 307 (0.33%)13 / 309 (0.97%)30 / 8 (0%)0
Cellulitis † A 1 / 307 (0.33%)22 / 309 (0.65%)20 / 8 (0%)0
Clostridium difficile colitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Cystitis † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Cytomegalovirus infection † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Device related infection † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Diverticulitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Empyema † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Erysipelas † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Fournier's gangrene † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Groin abscess † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Herpes zoster † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Herpes zoster meningoradiculitis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Infected fistula † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Infected lymphocele † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Infection † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Influenza † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Lower respiratory tract infection † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Pelvic infection † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Peritonitis † A 2 / 307 (0.65%)21 / 309 (0.32%)10 / 8 (0%)0
Pneumonia † A 1 / 307 (0.33%)17 / 309 (2.27%)70 / 8 (0%)0
Psoas abscess † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Pulmonary sepsis † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Pyelonephritis † A 4 / 307 (1.3%)42 / 309 (0.65%)40 / 8 (0%)0
Pyelonephritis acute † A 2 / 307 (0.65%)23 / 309 (0.97%)30 / 8 (0%)0
Pyometra † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Sepsis † A 8 / 307 (2.61%)85 / 309 (1.62%)50 / 8 (0%)0
Septic shock † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Staphylococcal bacteraemia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Urinary tract infection † A 16 / 307 (5.21%)1720 / 309 (6.47%)231 / 8 (12.5%)2
Urosepsis † A 2 / 307 (0.65%)24 / 309 (1.29%)50 / 8 (0%)0
Vascular device infection † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Wound infection † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Injury, poisoning and procedural complications
Ankle fracture † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Cystitis radiation † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Fall † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Femoral neck fracture † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Femur fracture † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
Fibula fracture † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Foot fracture † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Gastroenteritis radiation † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Gastrointestinal stoma complication † A 0 / 307 (0%)01 / 309 (0.32%)20 / 8 (0%)0
Hip fracture † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Humerus fracture † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Infusion related reaction † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Pelvic fracture † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Post procedural urine leak † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Procedural pneumothorax † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Radiation proctitis † A 4 / 307 (1.3%)62 / 309 (0.65%)20 / 8 (0%)0
Stoma site haemorrhage † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Tibia fracture † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Urinary tract stoma complication † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
Wrist fracture † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Investigations
Alanine aminotransferase increased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Aspartate aminotransferase increased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Blood alkaline phosphatase increased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Blood pressure increased † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Liver function test increased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Neutrophil count decreased † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Platelet count decreased † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Urine output decreased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Weight decreased † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Metabolism and nutrition disorders
Cachexia † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Decreased appetite † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Dehydration † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Diabetic ketoacidosis † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Electrolyte imbalance † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Hypocalcaemia † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Hypokalaemia † A 2 / 307 (0.65%)22 / 309 (0.65%)20 / 8 (0%)0
Hypovolaemia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Musculoskeletal and connective tissue disorders
Autoimmune myositis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Back pain † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Muscular weakness † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Myalgia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Myositis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Osteoporosis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Pain in extremity † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Cervix carcinoma † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Diffuse large B-cell lymphoma † A 0 / 307 (0%)00 / 309 (0%)01 / 8 (12.5%)1
Endometrial adenocarcinoma † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Metastases to central nervous system † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Ovarian cancer recurrent † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Tumour haemorrhage † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Nervous system disorders
Cerebellar infarction † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Cerebral ischaemia † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Cerebrovascular accident † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Embolic stroke † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Encephalitis autoimmune † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Headache † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Hemiparesis † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Hypoaesthesia † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Idiopathic intracranial hypertension † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Ischaemic stroke † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Paraesthesia † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Peripheral motor neuropathy † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Peripheral sensorimotor neuropathy † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Peripheral sensory neuropathy † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
Posterior reversible encephalopathy syndrome † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Seizure † A 3 / 307 (0.98%)30 / 309 (0%)00 / 8 (0%)0
Syncope † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Transient ischaemic attack † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Product Issues
Device dislocation † A 2 / 307 (0.65%)22 / 309 (0.65%)20 / 8 (0%)0
Device occlusion † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Stent malfunction † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Psychiatric disorders
Confusional state † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Delirium † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Renal and urinary disorders
Acute kidney injury † A 11 / 307 (3.58%)135 / 309 (1.62%)60 / 8 (0%)0
Bladder diverticulum † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Haematuria † A 4 / 307 (1.3%)54 / 309 (1.29%)40 / 8 (0%)0
Hydronephrosis † A 4 / 307 (1.3%)44 / 309 (1.29%)41 / 8 (12.5%)1
Nephrolithiasis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Nephropathy † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Postrenal failure † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Renal failure † A 1 / 307 (0.33%)13 / 309 (0.97%)30 / 8 (0%)0
Ureteric stenosis † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Urethral fistula † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Urinary tract obstruction † A 1 / 307 (0.33%)13 / 309 (0.97%)30 / 8 (0%)0
Urinoma † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Urogenital fistula † A 4 / 307 (1.3%)42 / 309 (0.65%)20 / 8 (0%)0
Reproductive system and breast disorders
Abnormal uterine bleeding † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Female genital tract fistula † A 8 / 307 (2.61%)810 / 309 (3.24%)101 / 8 (12.5%)1
Heavy menstrual bleeding † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Intermenstrual bleeding † A 2 / 307 (0.65%)21 / 309 (0.32%)10 / 8 (0%)0
Pelvic pain † A 1 / 307 (0.33%)13 / 309 (0.97%)30 / 8 (0%)0
Uterine haemorrhage † A 3 / 307 (0.98%)31 / 309 (0.32%)10 / 8 (0%)0
Vaginal fistula † A 1 / 307 (0.33%)12 / 309 (0.65%)20 / 8 (0%)0
Vaginal haemorrhage † A 5 / 307 (1.63%)54 / 309 (1.29%)50 / 8 (0%)0
Vulval ulceration † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Dyspnoea † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Epistaxis † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Oropharyngeal pain † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Pleurisy † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Pneumonitis † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Pneumothorax † A 1 / 307 (0.33%)11 / 309 (0.32%)10 / 8 (0%)0
Pulmonary embolism † A 4 / 307 (1.3%)46 / 309 (1.94%)60 / 8 (0%)0
Pulmonary haemorrhage † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Skin and subcutaneous tissue disorders
Dermatitis allergic † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Drug eruption † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Rash erythematous † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Rash maculo-papular † A 3 / 307 (0.98%)30 / 309 (0%)00 / 8 (0%)0
Skin ulcer † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Vascular disorders
Deep vein thrombosis † A 4 / 307 (1.3%)41 / 309 (0.32%)10 / 8 (0%)0
Embolism † A 2 / 307 (0.65%)22 / 309 (0.65%)20 / 8 (0%)0
Hypertension † A 0 / 307 (0%)03 / 309 (0.97%)30 / 8 (0%)0
Hypertensive urgency † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
Orthostatic hypotension † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Shock haemorrhagic † A 2 / 307 (0.65%)20 / 309 (0%)00 / 8 (0%)0
Subclavian vein thrombosis † A 0 / 307 (0%)01 / 309 (0.32%)10 / 8 (0%)0
Vena cava embolism † A 1 / 307 (0.33%)10 / 309 (0%)00 / 8 (0%)0
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 25.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Pembrolizumab+ChemotherapyPlacebo+ChemotherapyPembrolizumab (Second Course)
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 298 / 307 (97.07%)299 / 309 (96.76%)5 / 8 (62.5%)
Blood and lymphatic system disorders
Anaemia † A 181 / 307 (58.96%)263159 / 309 (51.46%)2471 / 8 (12.5%)1
Leukopenia † A 40 / 307 (13.03%)7233 / 309 (10.68%)551 / 8 (12.5%)1
Lymphopenia † A 15 / 307 (4.89%)297 / 309 (2.27%)71 / 8 (12.5%)1
Neutropenia † A 71 / 307 (23.13%)14358 / 309 (18.77%)1150 / 8 (0%)0
Thrombocytopenia † A 60 / 307 (19.54%)9460 / 309 (19.42%)1010 / 8 (0%)0
Ear and labyrinth disorders
Ear discomfort † A 0 / 307 (0%)02 / 309 (0.65%)21 / 8 (12.5%)1
Endocrine disorders
Hyperthyroidism † A 25 / 307 (8.14%)279 / 309 (2.91%)100 / 8 (0%)0
Hypothyroidism † A 59 / 307 (19.22%)6431 / 309 (10.03%)330 / 8 (0%)0
Gastrointestinal disorders
Abdominal pain † A 49 / 307 (15.96%)6451 / 309 (16.5%)770 / 8 (0%)0
Abdominal pain lower † A 16 / 307 (5.21%)1812 / 309 (3.88%)130 / 8 (0%)0
Abdominal pain upper † A 29 / 307 (9.45%)4230 / 309 (9.71%)400 / 8 (0%)0
Constipation † A 89 / 307 (28.99%)141101 / 309 (32.69%)1460 / 8 (0%)0
Diarrhoea † A 111 / 307 (36.16%)20193 / 309 (30.1%)1731 / 8 (12.5%)1
Dyspepsia † A 20 / 307 (6.51%)2315 / 309 (4.85%)190 / 8 (0%)0
Gastrooesophageal reflux disease † A 11 / 307 (3.58%)1113 / 309 (4.21%)141 / 8 (12.5%)1
Nausea † A 122 / 307 (39.74%)264135 / 309 (43.69%)2870 / 8 (0%)0
Rectal haemorrhage † A 16 / 307 (5.21%)2615 / 309 (4.85%)200 / 8 (0%)0
Stomatitis † A 22 / 307 (7.17%)2621 / 309 (6.8%)270 / 8 (0%)0
Vomiting † A 80 / 307 (26.06%)12684 / 309 (27.18%)1410 / 8 (0%)0
General disorders
Asthenia † A 63 / 307 (20.52%)12166 / 309 (21.36%)1280 / 8 (0%)0
Fatigue † A 89 / 307 (28.99%)14985 / 309 (27.51%)1500 / 8 (0%)0
Mucosal inflammation † A 23 / 307 (7.49%)3110 / 309 (3.24%)140 / 8 (0%)0
Oedema peripheral † A 31 / 307 (10.1%)3730 / 309 (9.71%)360 / 8 (0%)0
Pyrexia † A 51 / 307 (16.61%)7744 / 309 (14.24%)590 / 8 (0%)0
Infections and infestations
Nasopharyngitis † A 19 / 307 (6.19%)2510 / 309 (3.24%)121 / 8 (12.5%)1
Upper respiratory tract infection † A 13 / 307 (4.23%)1816 / 309 (5.18%)210 / 8 (0%)0
Urinary tract infection † A 67 / 307 (21.82%)11972 / 309 (23.3%)1070 / 8 (0%)0
Injury, poisoning and procedural complications
Gastroenteritis radiation † A 7 / 307 (2.28%)73 / 309 (0.97%)31 / 8 (12.5%)1
Infusion related reaction † A 17 / 307 (5.54%)2412 / 309 (3.88%)170 / 8 (0%)0
Investigations
Alanine aminotransferase increased † A 45 / 307 (14.66%)6728 / 309 (9.06%)361 / 8 (12.5%)1
Aspartate aminotransferase increased † A 34 / 307 (11.07%)5623 / 309 (7.44%)301 / 8 (12.5%)1
Blood alkaline phosphatase increased † A 27 / 307 (8.79%)3318 / 309 (5.83%)201 / 8 (12.5%)1
Blood creatinine increased † A 28 / 307 (9.12%)4334 / 309 (11%)420 / 8 (0%)0
Neutrophil count decreased † A 56 / 307 (18.24%)15248 / 309 (15.53%)1420 / 8 (0%)0
Platelet count decreased † A 49 / 307 (15.96%)9942 / 309 (13.59%)680 / 8 (0%)0
Weight decreased † A 33 / 307 (10.75%)3337 / 309 (11.97%)380 / 8 (0%)0
White blood cell count decreased † A 37 / 307 (12.05%)10922 / 309 (7.12%)620 / 8 (0%)0
Metabolism and nutrition disorders
Decreased appetite † A 62 / 307 (20.2%)9552 / 309 (16.83%)760 / 8 (0%)0
Hyperglycaemia † A 14 / 307 (4.56%)2019 / 309 (6.15%)281 / 8 (12.5%)1
Hypoalbuminaemia † A 17 / 307 (5.54%)1811 / 309 (3.56%)111 / 8 (12.5%)1
Hypokalaemia † A 30 / 307 (9.77%)4329 / 309 (9.39%)340 / 8 (0%)0
Hypomagnesaemia † A 27 / 307 (8.79%)3819 / 309 (6.15%)310 / 8 (0%)0
Hyponatraemia † A 20 / 307 (6.51%)2515 / 309 (4.85%)160 / 8 (0%)0
Hypoproteinaemia † A 3 / 307 (0.98%)40 / 309 (0%)01 / 8 (12.5%)1
Musculoskeletal and connective tissue disorders
Arthralgia † A 82 / 307 (26.71%)12877 / 309 (24.92%)1240 / 8 (0%)0
Back pain † A 44 / 307 (14.33%)5546 / 309 (14.89%)610 / 8 (0%)0
Bone pain † A 21 / 307 (6.84%)2218 / 309 (5.83%)220 / 8 (0%)0
Myalgia † A 57 / 307 (18.57%)9861 / 309 (19.74%)1151 / 8 (12.5%)1
Pain in extremity † A 37 / 307 (12.05%)5827 / 309 (8.74%)510 / 8 (0%)0
Nervous system disorders
Dizziness † A 22 / 307 (7.17%)2725 / 309 (8.09%)320 / 8 (0%)0
Dysgeusia † A 15 / 307 (4.89%)1720 / 309 (6.47%)240 / 8 (0%)0
Headache † A 50 / 307 (16.29%)7657 / 309 (18.45%)980 / 8 (0%)0
Neuropathy peripheral † A 81 / 307 (26.38%)10680 / 309 (25.89%)970 / 8 (0%)0
Paraesthesia † A 28 / 307 (9.12%)3826 / 309 (8.41%)340 / 8 (0%)0
Peripheral sensory neuropathy † A 70 / 307 (22.8%)8178 / 309 (25.24%)880 / 8 (0%)0
Psychiatric disorders
Insomnia † A 34 / 307 (11.07%)3527 / 309 (8.74%)291 / 8 (12.5%)1
Renal and urinary disorders
Dysuria † A 21 / 307 (6.84%)2623 / 309 (7.44%)290 / 8 (0%)0
Haematuria † A 20 / 307 (6.51%)2515 / 309 (4.85%)200 / 8 (0%)0
Incontinence † A 3 / 307 (0.98%)40 / 309 (0%)01 / 8 (12.5%)1
Leukocyturia † A 5 / 307 (1.63%)81 / 309 (0.32%)11 / 8 (12.5%)1
Proteinuria † A 51 / 307 (16.61%)7931 / 309 (10.03%)480 / 8 (0%)0
Reproductive system and breast disorders
Pelvic pain † A 16 / 307 (5.21%)1833 / 309 (10.68%)390 / 8 (0%)0
Vaginal discharge † A 17 / 307 (5.54%)1824 / 309 (7.77%)260 / 8 (0%)0
Vaginal haemorrhage † A 25 / 307 (8.14%)4032 / 309 (10.36%)401 / 8 (12.5%)1
Respiratory, thoracic and mediastinal disorders
Asthma † A 2 / 307 (0.65%)20 / 309 (0%)01 / 8 (12.5%)1
Cough † A 40 / 307 (13.03%)4832 / 309 (10.36%)401 / 8 (12.5%)1
Dyspnoea † A 22 / 307 (7.17%)2830 / 309 (9.71%)340 / 8 (0%)0
Epistaxis † A 31 / 307 (10.1%)5343 / 309 (13.92%)640 / 8 (0%)0
Oropharyngeal discomfort † A 0 / 307 (0%)00 / 309 (0%)01 / 8 (12.5%)1
Skin and subcutaneous tissue disorders
Alopecia † A 173 / 307 (56.35%)173179 / 309 (57.93%)1810 / 8 (0%)0
Dry skin † A 18 / 307 (5.86%)189 / 309 (2.91%)100 / 8 (0%)0
Pruritus † A 40 / 307 (13.03%)5826 / 309 (8.41%)390 / 8 (0%)0
Rash † A 47 / 307 (15.31%)6636 / 309 (11.65%)472 / 8 (25%)2
Rash maculo-papular † A 16 / 307 (5.21%)209 / 309 (2.91%)131 / 8 (12.5%)2
Vascular disorders
Hypertension † A 79 / 307 (25.73%)11470 / 309 (22.65%)1000 / 8 (0%)0
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 25.0
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Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator 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 will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Results Point of Contact:
Name/Official Title:
 Senior Vice President, Global Clinical Development
Organization:
 Merck Sharp & Dohme LLC
Phone:
 1-800-672-6372
Email:
 ClinicalTrialsDisclosure@merck.com
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