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)

Cervical Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03635567
• Other study ID #: 3475-826
• Secondary ID: MK-3475-826KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 25, 2018
• Est. completion date: June 4, 2024

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 617
• Est. completion date: June 4, 2024
• Est. primary completion date: October 3, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Paclitaxel
IV infusion
• Cisplatin
IV infusion
• Carboplatin
IV infusion

Biological:
• Bevacizumab
IV infusion

Drug:
• Placebo to pembrolizumab
IV infusion

Locations

Country	Name	City	State
Argentina	Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1006)	Berazategui	Buenos Aires
Argentina	Hospital Aleman ( Site 1005)	Buenos Aires
Argentina	Hospital de Oncologia Angel Roffo ( Site 1003)	Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming ( Site 1009)	Buenos Aires
Argentina	Centro Oncologico Riojano Integral ( Site 1004)	La Rioja
Argentina	Centro Medico San Roque ( Site 1001)	Tucuman
Australia	Flinders Medical Centre ( Site 1513)	Bedford Park	South Australia
Australia	Monash Health-Monash Medical Centre ( Site 1519)	Clayton
Australia	Mater Misericordiae Ltd Mater Cancer Care Centre ( Site 1521)	South Brisbane	Queensland
Australia	Royal North Shore Hospital ( Site 1514)	St Leonards	New South Wales
Australia	St John of God Subiaco Hospital ( Site 1512)	Subiaco	Western Australia
Canada	Tom Baker Cancer Centre ( Site 1728)	Calgary	Alberta
Canada	CIUSSS du Saguenay-Lac-St-Jean ( Site 1729)	Chicoutimi	Quebec
Canada	Queen Elizabeth II Health Sciences Centre ( Site 1731)	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre ( Site 1735)	Hamilton	Ontario
Canada	BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 1734)	Kelowna	British Columbia
Canada	London Regional Cancer Program - London HSC ( Site 1723)	London	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 1721)	Montreal	Quebec
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 1726)	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre ( Site 1736)	Ottawa	Ontario
Canada	CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 1724)	Quebec
Canada	CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 1730)	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre ( Site 1732)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 1733)	Toronto	Ontario
Canada	BC Cancer - Vancouver Center ( Site 1722)	Vancouver	British Columbia
Canada	CancerCare Manitoba ( Site 1725)	Winnipeg	Manitoba
Chile	Centro de Cancer Nuestra Senora de la Esperanza ( Site 1063)	Santiago
Chile	Fundacion Arturo Lopez Perez FALP ( Site 1061)	Santiago
Chile	Sociedad Oncovida S.A. ( Site 1069)	Santiago
Chile	Instituto Clinico Oncologico del Sur ( Site 1062)	Temuco
Chile	Oncocentro ( Site 1065)	Vina del Mar	Valparaiso
Colombia	Biomelab S A S ( Site 1104)	Barranquilla
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 1095)	Bogota	Cundinamarca
Colombia	Hemato Oncologos S.A. ( Site 1100)	Cali	Valle
Colombia	Oncomedica S.A. ( Site 1098)	Monteria
Colombia	Instituto Cancerologico de Narino Ltda ( Site 1097)	Pasto
Colombia	Sociedad de Oncologia y Hematologia del Cesar Ltda. ( Site 1103)	Valledupar	Cesar
France	Centre Jean Perrin ( Site 1181)	Clermont Ferrand
France	Institut Paoli Calmettes ( Site 1182)	Marseille
France	Groupe Hospitalier Broca Cochin Hotel Dieu ( Site 1183)	Paris
France	Centre Eugene Marquis ( Site 1187)	Rennes
France	Institut Curie - Centre Rene Huguenin ( Site 1185)	Saint-Cloud
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 1211)	Dresden
Germany	Universitaetsklinikum Duesseldorf ( Site 1220)	Duesseldorf
Germany	Universitatsklinikum Essen AoR ( Site 1213)	Essen
Germany	Universitatsklinikum Hamburg-Eppendorf ( Site 1212)	Hamburg
Germany	Gynoncological Practice Lueck. Schrader. Noeding ( Site 1224)	Hannover
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 1214)	Kiel
Germany	Rotkreuzklinikum Muenchen gGmbH. Studienzentrale Frauenklinik ( Site 1225)	Muenchen
Germany	Klinikum Oldenburg AoeR ( Site 1218)	Oldenburg
Germany	Universitaet Regensburg ( Site 1221)	Regensburg
Israel	Soroka Medical Center ( Site 1363)	Beer-Sheva
Israel	Rambam Medical Center ( Site 1364)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 1367)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 1366)	Jerusalem
Israel	Rabin Medical Center ( Site 1365)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 1361)	Ramat Gan
Israel	Sourasky Medical Center ( Site 1362)	Tel Aviv
Italy	Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 1243)	Aviano
Italy	A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1245)	Bolgna
Italy	Istituto Europeo di Oncologia ( Site 1250)	Milano
Italy	Istituto Nazionale Tumori ( Site 1251)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1242)	Napoli
Italy	Policlinico Universitario -Agostino Gemelli ( Site 1241)	Roma
Japan	Hyogo Cancer Center ( Site 1705)	Akashi	Hyogo
Japan	Saitama Medical University International Medical Center ( Site 1691)	Hidaka	Saitama
Japan	National Cancer Center Hospital East ( Site 1704)	Kashiwa	Chiba
Japan	The Jikei University Kashiwa Hospital ( Site 1701)	Kashiwa	Chiba
Japan	Kurume University Hospital ( Site 1692)	Kurume	Fukuoka
Japan	University of the Ryukyus Hospital ( Site 1706)	Nakagami-gun	Okinawa
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 1700)	Sapporo	Hokkaido
Japan	Iwate Medical University Hospital ( Site 1695)	Shiwa-gun	Iwate
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 1703)	Sunto-gun	Shizuoka
Japan	Keio University Hospital ( Site 1699)	Tokyo
Japan	National Cancer Center Hospital ( Site 1702)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 1698)	Tokyo
Japan	The Jikei University Hospital ( Site 1697)	Tokyo
Japan	Ehime University Hospital ( Site 1693)	Toon	Ehime
Korea, Republic of	Keimyung University Dongsan Medical Center ( Site 1603)	Daegu
Korea, Republic of	Asan Medical Center ( Site 1601)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1604)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1602)	Seoul
Mexico	Centro Estatal de Cancerologia de Chihuahua ( Site 1123)	Chihuahua
Mexico	Consultorio de Medicina Especializada del Sector Privado ( Site 1129)	Ciudad de Mexico
Mexico	CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 1127)	Ciudad de Mexico
Mexico	Medical Care and Research S.A. de C.V. ( Site 1135)	Merida	Yucatan
Mexico	Instituto Nacional de Cancerologia. ( Site 1130)	Mexico
Mexico	Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 1125)	San Pedro Garza Garcia
Mexico	Faicic S de RL de CV ( Site 1133)	Veracruz
Peru	Centro Medico Monte Carmelo ( Site 1156)	Arequipa
Peru	Hospital Nacional Arzobispo Loayza ( Site 1159)	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen ( Site 1158)	Lima
Peru	Hospital Nacional Maria Auxiliadora ( Site 1155)	Lima
Peru	Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 1157)	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 1153)	Lima
Peru	Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 1152)	Trujillo	La Libertad
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1331)	Kazan
Russian Federation	FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1334)	Moscow
Russian Federation	Medical Rehabilitation Center ( Site 1337)	Moscow
Russian Federation	Novosibirsk Regional Clinical Oncology Dispensary ( Site 1358)	Novosibirsk
Russian Federation	Municipal Clinical Oncology Center ( Site 1346)	Saint Petersburg
Russian Federation	National Research Ogarev Mordovia State University ( Site 1347)	Saransk
Russian Federation	National Medical Research Center of Oncology n.a. N. N. Petrov ( Site 1348)	St. Petersburg
Russian Federation	Tomsk Scientific Research Institute of Oncology ( Site 1360)	Tomsk
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1345)	Ufa
Spain	Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1276)	Badalona
Spain	Onkologikoa - Instituto Oncologico de San Sebastian ( Site 1275)	Doniostia - San Sebastian	Guipuzcoa
Spain	MD Anderson Cancer Center Madrid ( Site 1273)	Madrid
Spain	Hospital Quiron Madrid ( Site 1277)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen Macarena ( Site 1274)	Sevilla
Taiwan	Kaohsiung Veterans General Hospital ( Site 1632)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 1635)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 1634)	Taichung
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center ( Site 1636)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 1631)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 1633)	Taoyuan
Turkey	Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1457)	Adana
Turkey	Baskent Universitesi Ankara Hastanesi ( Site 1451)	Ankara
Turkey	Hacettepe University Medical Faculty ( Site 1459)	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi ( Site 1453)	Antalya
Turkey	Medeniyet University Goztepe Egitim ve Arastirma Hast. Merdivenkoy ( Site 1458)	Istanbul
Turkey	Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1456)	Izmir
Turkey	Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 1452)	Konya
Ukraine	City Clinical Hosp.4 of DCC ( Site 1482)	Dnipropetrovsk
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 1487)	Ivano-Frankivsk
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 1489)	Kharkiv
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 1484)	Kyiv
Ukraine	MI Odessa Regional Oncological Centre ( Site 1493)	Odesa
Ukraine	Medical Centre LLC Oncolife ( Site 1485)	Zaporizhzhya
United States	Alaska Women's Cancer Care ( Site 1770)	Anchorage	Alaska
United States	Georgia Cancer Center at Augusta University ( Site 1767)	Augusta	Georgia
United States	MUSC Hollings Cancer Center ( Site 1819)	Charleston	South Carolina
United States	Barbara Ann Karmanos Cancer Institute ( Site 1785)	Detroit	Michigan
United States	Henry Ford Health System ( Site 1810)	Detroit	Michigan
United States	West Cancer Center - East Campus ( Site 1763)	Germantown	Tennessee
United States	OSU Wexner Medical Center ( Site 1817)	Hilliard	Ohio
United States	Smilow Cancer Hospital at Yale New Haven ( Site 1809)	New Haven	Connecticut
United States	Columbia University Medical Center ( Site 1800)	New York	New York
United States	Mount Sinai Chelsea ( Site 1760)	New York	New York
United States	Cancer Institute of New Jersey at University Hospital ( Site 1762)	Newark	New Jersey
United States	University of Oklahoma- Stephenson Oklahoma Cancer Center ( Site 1784)	Oklahoma City	Oklahoma
United States	UC Irvine Health ( Site 1796)	Orange	California
United States	Arizona Oncology Associates, PC- HAL ( Site 8005)	Phoenix	Arizona
United States	Washington University School of Medicine ( Site 1779)	Saint Louis	Missouri
United States	Texas Oncology-San Antonio Medical Center ( Site 8001)	San Antonio	Texas
United States	Seattle Cancer Care Alliance ( Site 1777)	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute ( Site 1754)	Tampa	Florida
United States	Holy Name Medical Center ( Site 1776)	Teaneck	New Jersey
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1768)	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Colombia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine, 

References & Publications (1)

Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Tekin C, Li K, Keefe SM, Lorusso D; KEYNOTE-826 Investigators. First-Line — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to approximately 46 months
Primary	PFS Per RECIST 1.1 as Assessed by Investigator in All Participants	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever 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.	Up to approximately 46 months
Primary	PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS =10	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.	Up to approximately 46 months
Primary	Overall Survival (OS) in Participants With PD-L1 CPS =1	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.	Up to approximately 46 months
Primary	OS in All Participants	OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented.	Up to approximately 46 months
Primary	OS in Participants With PD-L1 CPS =10	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.	Up to approximately 46 months
Secondary	Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator	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.	Up to approximately 46 months
Secondary	Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator	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.	Up to approximately 46 months
Secondary	Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator	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.	12 months
Secondary	PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)	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.	Up to approximately 46 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	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.	Up to approximately 46 months
Secondary	Number of Participants Who Experienced a Serious AE (SAE)	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.	Up to approximately 46 months
Secondary	Number of Participants Who Experienced an Immune-related AE (irAE)	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.	Up to approximately 46 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an AE	The number of participants who discontinued study treatment due to an AE is presented.	Up to approximately 43 months
Secondary	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	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".	Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months

External Links

•   Merck Clinical Trials Information