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)

NCT03635567 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-826MK-3475-826KEYNOTE-8261841832018-001440-53
• Study Type: interventional
• Target: 617
• Locations: 19 countries
• Sites: 149

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).

Conditions

Cervical Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (9)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 46 months

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 46 months

• Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator

  12 months

• PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)

  Up to approximately 46 months

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 66 months

Study Arms (2)

Pembrolizumab+Chemotherapy

EXPERIMENTAL

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; Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin; Biological: Bevacizumab

Placebo+Chemotherapy

PLACEBO COMPARATOR

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; Drug: Cisplatin; Drug: Carboplatin; Biological: Bevacizumab; Drug: Placebo to pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab+Chemotherapy

Paclitaxel DRUG

IV infusion

Also known as: TAXOL®

Pembrolizumab+Chemotherapy; Placebo+Chemotherapy

Cisplatin DRUG

IV infusion

Also known as: PLATINOL®

Pembrolizumab+Chemotherapy; Placebo+Chemotherapy

Carboplatin DRUG

IV infusion

Also known as: PARAPLATIN®

Pembrolizumab+Chemotherapy; Placebo+Chemotherapy

Bevacizumab BIOLOGICAL

IV infusion

Also known as: AVASTIN®

Pembrolizumab+Chemotherapy; Placebo+Chemotherapy

Placebo to pembrolizumab DRUG

IV infusion

Also known as: Normal Saline or Dextrose solution

Placebo+Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (149)

Alaska Women's Cancer Care ( Site 1770)

Anchorage, Alaska, 99508, United States

Location

Arizona Oncology Associates, PC- HAL ( Site 8005)

Phoenix, Arizona, 85016, United States

Location

UC Irvine Health ( Site 1796)

Orange, California, 92868, United States

Location

Smilow Cancer Hospital at Yale New Haven ( Site 1809)

New Haven, Connecticut, 06510, United States

Location

H. Lee Moffitt Cancer Center and Research Institute ( Site 1754)

Tampa, Florida, 33612, United States

Location

Georgia Cancer Center at Augusta University ( Site 1767)

Augusta, Georgia, 30912, United States

Location

Barbara Ann Karmanos Cancer Institute ( Site 1785)

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System ( Site 1810)

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine ( Site 1779)

St Louis, Missouri, 63110, United States

Location

Cancer Institute of New Jersey at University Hospital ( Site 1762)

Newark, New Jersey, 07103, United States

Location

Holy Name Medical Center ( Site 1776)

Teaneck, New Jersey, 07666, United States

Location

Mount Sinai Chelsea ( Site 1760)

New York, New York, 10011, United States

Location

Columbia University Medical Center ( Site 1800)

New York, New York, 10032, United States

Location

OSU Wexner Medical Center ( Site 1817)

Hilliard, Ohio, 43026, United States

Location

University of Oklahoma- Stephenson Oklahoma Cancer Center ( Site 1784)

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1768)

Tulsa, Oklahoma, 74146, United States

Location

MUSC Hollings Cancer Center ( Site 1819)

Charleston, South Carolina, 29425, United States

Location

West Cancer Center - East Campus ( Site 1763)

Germantown, Tennessee, 38138, United States

Location

Texas Oncology-San Antonio Medical Center ( Site 8001)

San Antonio, Texas, 78240, United States

Location

Seattle Cancer Care Alliance ( Site 1777)

Seattle, Washington, 98109, United States

Location

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1006)

Berazategui, Buenos Aires, B1884BBF, Argentina

Location

Hospital Aleman ( Site 1005)

Buenos Aires, C1118AAT, Argentina

Location

Hospital de Oncologia Angel Roffo ( Site 1003)

Buenos Aires, C1417DTB, Argentina

Location

Instituto Medico Especializado Alexander Fleming ( Site 1009)

Buenos Aires, C1426ANZ, Argentina

Location

Centro Oncologico Riojano Integral ( Site 1004)

La Rioja, F5300COE, Argentina

Location

Centro Medico San Roque ( Site 1001)

San Miguel de Tucumán, T4000IAK, Argentina

Location

Royal North Shore Hospital ( Site 1514)

St Leonards, New South Wales, 2065, Australia

Location

Mater Misericordiae Ltd Mater Cancer Care Centre ( Site 1521)

South Brisbane, Queensland, 4101, Australia

Location

Flinders Medical Centre ( Site 1513)

Bedford Park, South Australia, 5042, Australia

Location

St John of God Subiaco Hospital ( Site 1512)

Subiaco, Western Australia, 6008, Australia

Location

Monash Health-Monash Medical Centre ( Site 1519)

Clayton, 3168, Australia

Location

Tom Baker Cancer Centre ( Site 1728)

Calgary, Alberta, T2N 4N2, Canada

Location

BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 1734)

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer - Vancouver Center ( Site 1722)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba ( Site 1725)

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Queen Elizabeth II Health Sciences Centre ( Site 1731)

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Juravinski Cancer Centre ( Site 1735)

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program - London HSC ( Site 1723)

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital Cancer Centre ( Site 1736)

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute ( Site 1733)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 1732)

Toronto, Ontario, M5G 2M9, Canada

Location

CIUSSS du Saguenay-Lac-St-Jean ( Site 1729)

Chicoutimi, Quebec, G7H 5H6, Canada

Location

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 1726)

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 1721)

Montreal, Quebec, H2X 3E4, Canada

Location

CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 1724)

Québec, Quebec, G1R 2J6, Canada

Location

CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 1730)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Oncocentro ( Site 1065)

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Fundacion Arturo Lopez Perez FALP ( Site 1061)

Santiago, 7500921, Chile

Location

Sociedad Oncovida S.A. ( Site 1069)

Santiago, 7510032, Chile

Location

Centro de Cancer Nuestra Senora de la Esperanza ( Site 1063)

Santiago, 8330024, Chile

Location

Instituto Clinico Oncologico del Sur ( Site 1062)

Temuco, 4810469, Chile

Location

Sociedad de Oncologia y Hematologia del Cesar Ltda. ( Site 1103)

Valledupar, Cesar Department, 200001, Colombia

Location

Instituto Nacional de Cancerologia E.S.E ( Site 1095)

Bogota, Cundinamarca, 111511, Colombia

Location

Hemato Oncologos S.A. ( Site 1100)

Cali, Valle del Cauca Department, 760046, Colombia

Location

Biomelab S A S ( Site 1104)

Barranquilla, 080002, Colombia

Location

Oncomedica S.A. ( Site 1098)

Montería, 230002, Colombia

Location

Instituto Cancerologico de Narino Ltda ( Site 1097)

Pasto, 520001, Colombia

Location

Centre Jean Perrin ( Site 1181)

Clermont-Ferrand, 63011, France

Location

Institut Paoli Calmettes ( Site 1182)

Marseille, 13009, France

Location

Groupe Hospitalier Broca Cochin Hotel Dieu ( Site 1183)

Paris, 75014, France

Location

Centre Eugene Marquis ( Site 1187)

Rennes, 35042, France

Location

Institut Curie - Centre Rene Huguenin ( Site 1185)

Saint-Cloud, 92210, France

Location

Universitaetsklinikum Carl Gustav Carus ( Site 1211)

Dresden, 01307, Germany

Location

Universitaetsklinikum Duesseldorf ( Site 1220)

Düsseldorf, 40225, Germany

Location

Universitatsklinikum Essen AoR ( Site 1213)

Essen, 45147, Germany

Location

Universitatsklinikum Hamburg-Eppendorf ( Site 1212)

Hamburg, 20251, Germany

Location

Gynoncological Practice Lueck. Schrader. Noeding ( Site 1224)

Hanover, 30177, Germany

Location

Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 1214)

Kiel, 24105, Germany

Location

Rotkreuzklinikum Muenchen gGmbH. Studienzentrale Frauenklinik ( Site 1225)

München, 80637, Germany

Location

Klinikum Oldenburg AoeR ( Site 1218)

Oldenburg, 26133, Germany

Location

Universitaet Regensburg ( Site 1221)

Regensburg, 93053, Germany

Location

Soroka Medical Center ( Site 1363)

Beersheba, 8410101, Israel

Location

Rambam Medical Center ( Site 1364)

Haifa, 3525408, Israel

Location

Shaare Zedek Medical Center ( Site 1366)

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 1367)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center ( Site 1365)

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center ( Site 1361)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 1362)

Tel Aviv, 6423906, Israel

Location

Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 1243)

Aviano, 33081, Italy

Location

A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1245)

Bolgna, 40138, Italy

Location

Istituto Nazionale Tumori ( Site 1251)

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia ( Site 1250)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1242)

Naples, 80131, Italy

Location

Policlinico Universitario -Agostino Gemelli ( Site 1241)

Roma, 00168, Italy

Location

The Jikei University Kashiwa Hospital ( Site 1701)

Kashiwa, Chiba, 277-8567, Japan

Location

National Cancer Center Hospital East ( Site 1704)

Kashiwa, Chiba, 277-8577, Japan

Location

Ehime University Hospital ( Site 1693)

Tōon, Ehime, 791-0295, Japan

Location

Kurume University Hospital ( Site 1692)

Kurume, Fukuoka, 830-0011, Japan

Location

National Hospital Organization Hokkaido Cancer Center ( Site 1700)

Sapporo, Hokkaido, 003-0804, Japan

Location

Hyogo Cancer Center ( Site 1705)

Akashi, Hyōgo, 673-8558, Japan

Location

Iwate Medical University Hospital ( Site 1695)

Shiwa-gun, Iwate, 028-3695, Japan

Location

University of the Ryukyus Hospital ( Site 1706)

Nakagami-gun, Okinawa, 903-0215, Japan

Location

Saitama Medical University International Medical Center ( Site 1691)

Hidaka, Saitama, 350-1298, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute ( Site 1703)

Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital ( Site 1702)

Tokyo, 104-0045, Japan

Location

The Jikei University Hospital ( Site 1697)

Tokyo, 105-8471, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 1698)

Tokyo, 135-8550, Japan

Location

Keio University Hospital ( Site 1699)

Tokyo, 160-8582, Japan

Location

Medical Care and Research S.A. de C.V. ( Site 1135)

Mérida, Yucatán, 97070, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua ( Site 1123)

Chihuahua City, 31000, Mexico

Location

Consultorio de Medicina Especializada del Sector Privado ( Site 1129)

Mexico City, 03100, Mexico

Location

CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 1127)

Mexico City, 06100, Mexico

Location

Instituto Nacional de Cancerologia. ( Site 1130)

México, 14080, Mexico

Location

Centro de Urologia Avanzada del Noreste S.A. de C.V. ( Site 1125)

San Pedro Garza García, 66269, Mexico

Location

Faicic S de RL de CV ( Site 1133)

Veracruz, 91900, Mexico

Location

Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 1152)

Trujillo, La Libertad, 13006, Peru

Location

Centro Medico Monte Carmelo ( Site 1156)

Arequipa, 04001, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen ( Site 1158)

Lima, 15033, Peru

Location

Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 1157)

Lima, 15036, Peru

Location

Instituto Nacional de Enfermedades Neoplasicas ( Site 1153)

Lima, 15038, Peru

Location

Hospital Nacional Arzobispo Loayza ( Site 1159)

Lima, 15082, Peru

Location

Hospital Nacional Maria Auxiliadora ( Site 1155)

Lima, 15801, Peru

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1331)

Kazan', 420029, Russia

Location

FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1334)

Moscow, 115478, Russia

Location

Medical Rehabilitation Center ( Site 1337)

Moscow, 125367, Russia

Location

Novosibirsk Regional Clinical Oncology Dispensary ( Site 1358)

Novosibirsk, 630108, Russia

Location

National Medical Research Center of Oncology n.a. N. N. Petrov ( Site 1348)

Saint Petersburg, 197758, Russia

Location

Municipal Clinical Oncology Center ( Site 1346)

Saint Petersburg, 198255, Russia

Location

National Research Ogarev Mordovia State University ( Site 1347)

Saransk, 430005, Russia

Location

Tomsk Scientific Research Institute of Oncology ( Site 1360)

Tomsk, 634028, Russia

Location

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1345)

Ufa, 450054, Russia

Location

Keimyung University Dongsan Medical Center ( Site 1603)

Daegu, 42601, South Korea

Location

Seoul National University Hospital ( Site 1602)

Seoul, 03080, South Korea

Location

Asan Medical Center ( Site 1601)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1604)

Seoul, 06351, South Korea

Location

Onkologikoa - Instituto Oncologico de San Sebastian ( Site 1275)

Doniostia - San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Quiron Madrid ( Site 1277)

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1276)

Badalona, 08916, Spain

Location

MD Anderson Cancer Center Madrid ( Site 1273)

Madrid, 28033, Spain

Location

Hospital Universitario Virgen Macarena ( Site 1274)

Seville, 41009, Spain

Location

Kaohsiung Veterans General Hospital ( Site 1632)

Kaohsiung City, 813, Taiwan

Location

China Medical University Hospital ( Site 1635)

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital ( Site 1634)

Taichung, 40705, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center ( Site 1636)

Taipei, 112, Taiwan

Location

Taipei Veterans General Hospital ( Site 1631)

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation. Linkou ( Site 1633)

Taoyuan District, 33305, Taiwan

Location

Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1457)

Adana, 01250, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty ( Site 1459)

Ankara, 06230, Turkey (Türkiye)

Location

Baskent Universitesi Ankara Hastanesi ( Site 1451)

Ankara, 06490, Turkey (Türkiye)

Location

Akdeniz Universitesi Tip Fakultesi ( Site 1453)

Antalya, 07059, Turkey (Türkiye)

Location

Medeniyet University Goztepe Egitim ve Arastırma Hast. Merdivenkoy ( Site 1458)

Istanbul, 34722, Turkey (Türkiye)

Location

Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1456)

Izmir, 35040, Turkey (Türkiye)

Location

Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 1452)

Konya, 42080, Turkey (Türkiye)

Location

City Clinical Hosp.4 of DCC ( Site 1482)

Dnipropetrovsk, 49102, Ukraine

Location

MI Precarpathian Clinical Oncology Center ( Site 1487)

Ivano-Frankivsk, 76018, Ukraine

Location

Communal non profit enterprise Regional Clinical Oncology Center ( Site 1489)

Kharkiv, 61070, Ukraine

Location

National Cancer Institute of the MoH of Ukraine ( Site 1484)

Kyiv, 03022, Ukraine

Location

MI Odessa Regional Oncological Centre ( Site 1493)

Odesa, 65055, Ukraine

Location

Medical Centre LLC Oncolife ( Site 1485)

Zaporizhzhya, 69104, Ukraine

Location

Related Publications (6)

• 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 Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826. J Clin Oncol. 2023 Dec 20;41(36):5505-5511. doi: 10.1200/JCO.23.00914. Epub 2023 Nov 1.

  PMID: 37910822 RESULT

• Kim YM, Nishio S, Kim SI, Hasegawa K, Dubot C, Caceres MV, Tewari KS, Lorusso D, Lee JW, Liou WS, Li K, Tekin C, Colombo N, Monk BJ. Pembrolizumab plus chemotherapy with or without bevacizumab in East Asian participants with persistent, recurrent, or metastatic cervical cancer: results from KEYNOTE-826 final analysis. J Gynecol Oncol. 2025 Jul;36(4):e110. doi: 10.3802/jgo.2025.36.e110.

  PMID: 40590325 DERIVED

• Monk BJ, van Mens S, Hale O, Boer J, van Hees F, Swami S, Muston D, Tekin C, Keefe S, Monberg M. Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States. Oncol Ther. 2025 Mar;13(1):85-98. doi: 10.1007/s40487-024-00311-5. Epub 2024 Nov 5.

  PMID: 39499492 DERIVED

• Tewari KS, Colombo N, Monk BJ, 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, Toker S, Keefe SM, Lorusso D. Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial. JAMA Oncol. 2024 Feb 1;10(2):185-192. doi: 10.1001/jamaoncol.2023.5410.

  PMID: 38095881 DERIVED

• Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yanez E, Gumus M, Hurtado de Mendoza MO, Samouelian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. doi: 10.1016/S1470-2045(23)00052-9. Epub 2023 Mar 3.

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• Colombo N, Dubot C, Lorusso D, Caceres MV, Hasegawa K, Shapira-Frommer R, Tewari KS, Salman P, Hoyos Usta E, Yanez E, Gumus M, Olivera Hurtado de Mendoza M, Samouelian V, Castonguay V, Arkhipov A, Toker S, Li K, Keefe SM, Monk BJ; KEYNOTE-826 Investigators. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 Nov 11;385(20):1856-1867. doi: 10.1056/NEJMoa2112435. Epub 2021 Sep 18.

  PMID: 34534429 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Paclitaxel; Cisplatin; Carboplatin; Bevacizumab; Saline Solution

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 17, 2018
• Study Start: October 25, 2018
• Primary Completion: October 3, 2022
• Study Completion: June 4, 2024
• Last Updated: February 4, 2026
• Results First Posted: October 12, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

JP (14); UA (6); IL (7); FR (5); TW (6); TU (7); DE (9); CA (15); RU (9); AU (5); US (20); CO (6); AR (6); KR (4); CL (5); PE (7); IT (6); ME (7); ES (5)