Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65)
Ovarian Cancer, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
Inclusion Criteria:
- Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
- Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
- Has provided documented informed consent for the study.
- Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
- Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
- For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
- Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
- Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
- Have adequate organ function.
Exclusion Criteria:
- Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
- Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
- Has prior disease progression on weekly paclitaxel alone.
- Has received >2 prior lines of systemic therapy for OC.
- Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
- Has received prior radiation therapy within 2 weeks of start of study intervention.
- Has not recovered adequately from surgery and/or any complications from the surgery.
- Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- 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 history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
- Has had an allogenic tissue/solid organ transplant.
For bevacizumab treatment
- Has uncontrolled hypertension.
- Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
- Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
Sites / Locations
- HonorHealth ( Site 0041)
- Marin Cancer Care ( Site 0055)
- Pacific Cancer Care ( Site 0028)
- Eisenhower Medical Center ( Site 0067)
- Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0004)
- University of Florida College of Medicine-UF Health Cancer Center/Clinical Trials Office ( Site 0054
- Sarasota Memorial Hospital ( Site 0018)
- Moffitt Cancer Center ( Site 0033)
- Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0005)
- Advocate Medical Group-Oncology ( Site 0049)
- Parkview Research Center at Parkview Regional Medical Center ( Site 0027)
- St. Vincent Hospital and Health Care Center, Inc ( Site 0032)
- Saint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0040)
- WK Physicians Network / Hematology Oncology Associates ( Site 0034)
- Mercy Medical Center - Baltimore-Medical Oncology and Hematology ( Site 0015)
- University of Massachusetts Chan Medical School-Division of Gynecologic Oncology ( Site 0003)
- John Theurer Cancer Center at Hackensack University Medical Center ( Site 0007)
- Roswell Park Cancer Institute ( Site 0039)
- Columbia University Medical Center ( Site 0010)
- Novant Health Presbyterian Medical Center ( Site 0029)
- Duke Cancer Institute ( Site 0038)
- Novant Health Forsyth Medical Center ( Site 0057)
- Aultman Hospital-Oncology Clinical Trials ( Site 0009)
- MetroHealth Medical Center-Cancer Care Center ( Site 0047)
- Providence Portland Medical Center ( Site 0048)
- University of Pittsburgh Medical Center Magee-Womens Hospital ( Site 0024)
- Sanford Cancer Center ( Site 0064)
- The West Clinic, PLLC dba West Cancer Center ( Site 0058)
- Texas Oncology - Dallas (Presbyterian) ( Site 0065)
- Texas Oncology - The Woodlands_Lee ( Site 0043)
- Inova Schar Cancer Institute ( Site 0019)
- Westmead Hospital-Department of Gynaecological Oncology ( Site 0201)
- Gallipoli Medical Research Foundation-GMRF CTU ( Site 0202)
- Epworth Freemasons ( Site 0204)
- St. John of God Subiaco Hospital ( Site 0203)
- Institut Jules Bordet-Medicine Oncology ( Site 0302)
- UZ Gent-Medical oncology ( Site 0301)
- UZ Leuven ( Site 0303)
- AZ Groeninge Campus Kennedylaan-Oncology ( Site 0305)
- Hospital Araújo Jorge ( Site 0401)
- Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0404)
- ANIMI - Unidade de Tratamento Oncologico ( Site 0408)
- BP - A Beneficencia Portuguesa de São Paulo ( Site 0403)
- Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0405)
- Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA-Pesquisa Clinica HC II ( Site 0402)
- Tom Baker Cancer Center ( Site 0511)
- BC Cancer Abbotsford ( Site 0512)
- BC Cancer Victoria ( Site 0513)
- Kingston Health Sciences Centre-Kingston General Hospital Si-Oncology and/or Hematology - Gynecolog
- Sunnybrook Health Sciences - Odette Cancer Centre ( Site 0508)
- CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0501)
- Jewish General Hospital ( Site 0505)
- McGill University Health Centre ( Site 0502)
- Saskatoon Cancer Center ( Site 0510)
- Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0
- James Lind Centro de Investigación del Cáncer ( Site 0602)
- CIDO SpA-Oncology ( Site 0608)
- Clínica Puerto Montt ( Site 0601)
- Oncovida ( Site 0603)
- Instituto de Radiomedicina-hemato-oncologia ( Site 0604)
- Clínica Vespucio-Hemato - Ocology ( Site 0607)
- Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 0609)
- Bradfordhill ( Site 0605)
- Anhui Provincial Hospital-Obstetrics and Gynecology ( Site 0709)
- Beijing Cancer hospital ( Site 0711)
- Beijing Peking Union Medical College Hospital-Gynecological center of tumor ( Site 0702)
- Fujian Provincial Cancer Hospital ( Site 0713)
- Lanzhou university second hospital ( Site 0734)
- Zhujiang Hospital ( Site 0739)
- Affiliated Hospital of Guangdong Medical University ( Site 0743)
- Guangxi Medical University Affiliated Tumor Hospital ( Site 0717)
- Hainan General Hospital ( Site 0736)
- Henan Cancer Hospital ( Site 0718)
- Wuhan Union Hospital-Medical Oncology ( Site 0735)
- Hubei Cancer Hospital-Hubei Cancer Hospital ( Site 0708)
- Xiangya Hospital Central South University-Gynecology ( Site 0705)
- Hunan Cancer Hospital ( Site 0704)
- Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Oncology (
- Zhongda Hospital Southeast University ( Site 0723)
- Jiangxi Maternal and Child Health Hospital-Oncology Department ( Site 0716)
- The First Hospital of Jilin University ( Site 0710)
- Shandong Cancer Hospital-Oncology Department ( Site 0733)
- LinYi Cancer Hospital ( Site 0731)
- Obstetrics & Gynecology Hospital of Fudan University ( Site 0715)
- Fudan University Shanghai Cancer Center-Gynecologic Oncology Department ( Site 0701)
- Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 0744)
- West China Second University Hospital Sichuan University ( Site 0740)
- Tianjin Central Hosptial of Gynecology Obstetrics ( Site 0737)
- Tianjin Medical University Cancer Institute and Hospital ( Site 0720)
- Yunnan Province Cancer Hospital-Gynecology Department ( Site 0714)
- The Affiliated Women's Hospital of Zhejiang University-Obstetrics and Gynecology ( Site 0741)
- The First Affiliated Hospital of Wenzhou Medical University-Gynecology ( Site 0706)
- Fundación Colombiana de Cancerología Clínica Vida ( Site 0808)
- Clinica de la Costa LTDA-Clinical Research Oncology & Hematology -Pediatric ( Site 0809)
- Clínica Universitaria Colombia ( Site 0806)
- Oncologos del Occidente ( Site 0807)
- Hemato Oncologos SA ( Site 0801)
- Aalborg Universitetshospital, Syd ( Site 0901)
- Turku University Hospital-Department of Obstetrics and Gynecology ( Site 1001)
- Centre Hospitalier Régional Universitaire de Brest - Hôpital-Institut de cancérologie et hématologi
- Centre François Baclesse-Recherche clinique ( Site 2904)
- Centre Hospitalier Universitaire de Limoges - Hôpital Dupuytren-oncologie ( Site 2907)
- Institut Curie - site Saint-Cloud ( Site 2909)
- Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer-Medical Oncology ( Site 2901)
- Centre de Cancérologie du Grand Montpellier ( Site 2908)
- Hôpital privé du Confluent SAS-Service d'oncologie médicale ( Site 2905)
- Universitaetsklinikum Erlangen-Klinik für Gynäkologie und Geburtshilfe ( Site 1205)
- Universitätsklinikum Bonn-Gynaecological oncology ( Site 1203)
- Universitaetsklinikum Duesseldorf-Klinik für Frauenheilkunde & Geburtshilfe ( Site 1204)
- Zentrum fuer ambulante gynaekologische Onkologie (ZAGO) ( Site 1207)
- CaritasKlinikum Saarbrücken St. Theresia ( Site 1211)
- Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Frauenheilkunde und Gebur
- Universitätsklinikum Leipzig-Department of Gynecology and Obstetrics ( Site 1213)
- Charité Campus Virchow-Klinikum ( Site 1201)
- Asklepios Kliniken Hamburg-Asklepios Klinik Barmbek ( Site 1214)
- St. James's Hospital-Cancer clinical trials office ( Site 2821)
- Emek Medical Center-Gyn-Onc ( Site 1406)
- Soroka Medical Center ( Site 1404)
- Rambam Health Care Campus-Gyneco-oncology unit ( Site 1402)
- Shaare Zedek Medical Center ( Site 1405)
- Rabin Medical Center ( Site 1401)
- Sheba Medical Center ( Site 1407)
- Sourasky Medical Center ( Site 1403)
- IRCCS - AOU di Bologna-SSD Oncologia medica Addarii ( Site 1501)
- Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1503)
- Ospedale San Gerardo-ASST Monza-Oncologia ( Site 1508)
- ASST Grande Ospedale Metropolitano Niguarda ( Site 1505)
- Ospedale Mauriziano-Ginecologia e Ostetricia ( Site 1507)
- Azienda Ospedaliera Spedali Civili di Brescia ( Site 1504)
- Istituto Europeo di Oncologia IRCCS-Divisione di Ginecologia Oncologica ( Site 1502)
- Aichi Cancer Center Hospital ( Site 1610)
- National Cancer Center Hospital East ( Site 1609)
- National Hospital Organization Shikoku Cancer Center ( Site 1603)
- Ehime University Hospital ( Site 1606)
- Kurume University Hospital ( Site 1607)
- Hokkaido University Hospital ( Site 1604)
- Iwate Medical University Hospital ( Site 1613)
- Nippon Medical School Musashi Kosugi Hospital ( Site 1614)
- Saitama Medical University International Medical Center ( Site 1601)
- Shizuoka Cancer Center ( Site 1611)
- National Cancer Center Hospital ( Site 1612)
- Japanese Foundation for Cancer Research ( Site 1605)
- Osaka International Cancer Institute ( Site 1602)
- Seoul National University Hospital ( Site 2302)
- Severance Hospital, Yonsei University Health System-Gynecologic cancer center ( Site 2303)
- Asan Medical Center-Division of Gynecologic Oncology, Dept. of Obstetrics & Gynecology ( Site 2304)
- Gangnam Severance Hospital ( Site 2301)
- Investigación Oncofarmacéutica-Investigación clínica ( Site 1706)
- COI Centro Oncologico Internacional S.A.P.I. de C.V.-Investigation Unit COI ( Site 1703)
- INSTITUTO NACIONAL DE CANCEROLOGIA ( Site 1701)
- iCan Oncology Center Centro Medico AVE ( Site 1704)
- Centro de Investigacion Clinica de Oaxaca ( Site 1705)
- Radboudumc ( Site 1802)
- Leids Universitair Medisch Centrum-Medical Oncology ( Site 1801)
- Erasmus Medisch Centrum-Medical Oncology ( Site 1803)
- Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 1804)
- Auckland City Hospital ( Site 1901)
- Universitetssykehuset Nord-Norge HF-Kreftavdelingen ( Site 2001)
- Szpital Kliniczny im. Księżnej Anny Mazowieckiej ( Site 2103)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Gynecological Oncology Department ( Sit
- Bialostockie Centrum Onkologii-Oddzial Onkologii Ginekologicznej ( Site 2106)
- Uniwersytecki Szpital Kliniczny w Bialymstoku-Uniwersyteckie Centrum Onkologii ( Site 2104)
- Uniwersyteckie Centrum Kliniczne-Klinika Ginekologii, Ginekologii Onkologicznej i Endokrynologii Gi
- Narodowy Instytut Onkologii - Oddzial w Gliwicach-III Klinika Radioterapii i Chemioterapii ( Site 21
- Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 2107)
- Szpital Kliniczny im. Heliodora Święcickiego Uniwersytetu Me-Oddzial Ginekologii Onkologicznej ( Sit
- Chelyabinsk Regional Clinical Oncology Dispensary-Chelyabinsk Regional Clinical Oncology Dispensary
- Ogarev Mordovia State University ( Site 2209)
- Moscow City Oncology Hospital #62 ( Site 2214)
- Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF-Chemotherapy #2 ( Site 2211)
- SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY-Oncogynecology Department ( Site 2216)
- cukurova universty ( Site 2706)
- Istanbul Universitesi Cerrahpasa ( Site 2709)
- Ege University Medicine of Faculty ( Site 2702)
- Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 2704)
- Ankara University Hospital Cebeci ( Site 2701)
- Baskent Universitesi Ankara Hastanesi ( Site 2707)
- Bezmialem Vakf Üniversitesi-Oncology ( Site 2705)
- T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma
- Brighton and Sussex University Hospitals NHS Trust ( Site 2803)
- Addenbrooke's Hospital ( Site 2808)
- The Royal Cornwall Hospital ( Site 2804)
- Westmorland General Hospital ( Site 2815)
- Ninewells Hospital and Medical School ( Site 2826)
- Leicester Royal Infirmary-HOPE Clinical Trials Unit ( Site 2812)
- Hammersmith Hospital-Medical Oncology ( Site 2818)
- Velindre Cancer Centre ( Site 2805)
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Pembrolizumab + paclitaxel ± bevacizumab
Placebo + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
Participants receive placebo via IV infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.