Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)

Ovarian Cancer Clinical Trial

Official title:

A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First-Line Treatment of BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001 / ENGOT-ov43 / GOG-3036)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03740165
• Other study ID #: 7339-001
• Secondary ID: ENGOT-ov43MK-733
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 18, 2018
• Est. completion date: May 29, 2026

Study information

• Verified date: December 2023
• 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 treatment with carboplatin/paclitaxel* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer. The primary study hypotheses are that the combination of pembrolizumab plus carboplatin/paclitaxel* followed by continued pembrolizumab and maintenance olaparib is superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in participants with programmed death-ligand 1 (PD-L1)-positive tumors (Combined Positive Score [CPS]≥10) and in all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect to PFS per RECIST 1.1 in participants with PD-L1-positive tumors (CPS≥10) and in all participants.

Description:

Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel*, participants will be randomly assigned in to one of three treatment arms: - Pembrolizumab + Olaparib, - Pembrolizumab + Placebo for Olaparib - Placebo for Pembrolizumab + Placebo for Olaparib - At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected: 1. up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle 2. up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or 3. up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle. Docetaxel may be considered for participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after consultation with the Sponsor. The recommended dose as determined by the Scottish Gynaecological Cancer Trials Group is Docetaxel 75 mg/m^2 Q3W plus carboplatin AUC 5 Q3W.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1367
• Est. completion date: May 29, 2026
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
• Has just completed primary debulking surgery or is eligible for primary debulking surgery or is a potential candidate for interval debulking surgery
• Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
• Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125) (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor markers status prior to randomization
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 3 days prior to Day 1 of Cycle 1
• Female participants are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) Is a WOCBP and using a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the Treatment Period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours (serum) before the first dose of study treatment. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Has adequate organ function

Exclusion Criteria:

• Has mucinous, germ cell, or borderline tumor of the ovary
• Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
• Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
• Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
• Has a known additional malignancy that is progressing or has required active treatment in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical carcinoma in situ) that has undergone potentially curative therapy are not excluded.
• Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period
• Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to randomization. Stable brain metastases should be established prior to the first dose of study medication lead-in chemotherapy
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing >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 the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) Note: 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 known history of active tuberculosis (TB; Bacillus Tuberculosis)
• Has an active infection requiring systemic therapy
• Has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in period
• Is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
• Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer <6 months prior to screening
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Testing for hepatitis B or hepatitis C is required at screening only if mandated by local health authority. Note: Participants with a history of hepatitis B but who are HBsAg negative are eligible for the study
• Is either unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption)
• Has uncontrolled hypertension
• Has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or GI perforation, related to underlying EOC (for participants receiving bevacizumab)
• Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to randomization (for participants receiving bevacizumab)
• Is a WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to Day 1 of Cycle 1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study, starting with screening through 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy
• Has received prior treatment for any stage of OC, including radiation or systemic anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, investigational therapy)
• Has received prior therapy with an anti-Programmed Cell Death-1 (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 antigen-4 [CTLA-4], OX 40, CD137)
• Has received prior therapy with either olaparib or any other poly(adenosine-ribose) polymerase (PARP) inhibitor
• Has intraperitoneal chemotherapy planned or has been administered as first-line therapy
• Has received a live vaccine within 30 days prior to the first dose of study treatment on Day 1 of Cycle 1
• Has severe hypersensitivity (=Grade 3) to pembrolizumab, olaparib, carboplatin, paclitaxel or bevacizumab (if using) and/or any of their excipients
• Is currently receiving either strong (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
• Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
• Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks (28 days) of starting chemotherapy in the Lead-in Period
• Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions or participant has congenital long QT syndrome
• Has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation
• Either has had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Placebo for pembrolizumab
IV infusion
• Carboplatin
IV infusion
• Paclitaxel
IV infusion
• Olaparib
Oral tablet
• Placebo for olaparib
Oral tablet

Biological:
• Bevacizumab
IV infusion

Drug:
• Docetaxel
IV infusion

Locations

Country	Name	City	State
Australia	Ballarat Health Services ( Site 2202)	Ballarat	Victoria
Australia	Cairns and Hinterland Hospital and Health Service ( Site 2201)	Cairns	Queensland
Australia	Monash Health ( Site 2204)	Clayton	Victoria
Australia	St George Hospital ( Site 2207)	Kogarah	New South Wales
Australia	Sunshine Hospital. ( Site 2205)	St Albans	Victoria
Belgium	Imelda Ziekenhuis Bonheiden ( Site 0301)	Bonheiden	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc ( Site 0312)	Brussels	Bruxelles-Capitale, Region De
Belgium	Grand Hopital de Charleroi ( Site 0302)	Charleroi	Hainaut
Belgium	AZ Maria Middelares Gent ( Site 0300)	Gent	Oost-Vlaanderen
Belgium	UZ Gent ( Site 0307)	Gent	Oost-Vlaanderen
Belgium	Jessa Ziekenhuis ( Site 0309)	Hasselt	Limburg
Belgium	UZ Leuven Campus Gasthuisberg ( Site 0306)	Leuven	Antwerpen
Belgium	Centre Hospitalier de l'Ardenne ( Site 0303)	Libramont	Luxembourg
Belgium	CHU de Liege ( Site 0310)	Liège	Liege
Brazil	Hospital Erasto Gaertner ( Site 2716)	Curitiba	Parana
Brazil	Instituto do Cancer do Ceara ( Site 2707)	Fortaleza	Ceara
Brazil	Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 2708)	Goiania	Goias
Brazil	Hospital de Caridade de Ijui ( Site 2712)	Ijui	Rio Grande Do Sul
Brazil	Hospital Bruno Born ( Site 2704)	Lajeado	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora Da Conceicao ( Site 2703)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Cancer Hospital do Cancer II ( Site 2700)	Rio de Janeiro
Brazil	Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 2706)	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2714)	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 2710)	Sao Paulo
Canada	Tom Baker Cancer Centre ( Site 0200)	Calgary	Alberta
Canada	CIUSSS du Saguenay-Lac-St-Jean ( Site 0218)	Chicoutimi	Quebec
Canada	Kingston Health Sciences Centre ( Site 0207)	Kingston	Ontario
Canada	The Credit Valley Hospital ( Site 0206)	Mississauga	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0208)	Montreal	Quebec
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0219)	Montreal	Quebec
Canada	Royal Victoria Hospital McGill University Health Centre ( Site 0211)	Montreal	Quebec
Canada	Princess Margaret Hospital.. ( Site 0202)	Toronto	Ontario
Chile	Centro Oncologico Antofagasta ( Site 2804)	Antofagasta
Chile	Fundacion Arturo Lopez Perez FALP ( Site 2800)	Santiago	Region M. De Santiago
Chile	Iram Cancer Research ( Site 2809)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 2805)	Santiago	Region M. De Santiago
Chile	Sociedad Oncovida S.A. ( Site 2807)	Santiago	Region M. De Santiago
Chile	Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 2808)	Temuco	Araucania
Chile	Centro Investigación del Cáncer James Lind ( Site 2810)	Temuco	Araucania
Chile	Oncocentro ( Site 2801)	Vina del Mar	Valparaiso
Colombia	Biomelab S A S ( Site 2900)	Barranquilla	Atlantico
Colombia	Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2912)	Bogota	Distrito Capital De Bogota
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 2910)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 2909)	Cali	Valle Del Cauca
Colombia	Hemato Oncologos S.A. ( Site 2906)	Cali	Valle Del Cauca
Colombia	Oncomedica S.A. ( Site 2911)	Monteria	Cordoba
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2913)	Valledupar	Cesar
Czechia	Fakultni nemocnice Brno ( Site 0404)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc ( Site 0402)	Olomouc
Czechia	Fakultni nemocnice Ostrava ( Site 0403)	Ostrava-Poruba	Moravskoslezsky Kraj
Czechia	Nemocnice Na Bulovce ( Site 0401)	Praha	Praha, Hlavni Mesto
Czechia	Vseobecna fakultni nemocnice v Praze ( Site 0400)	Praha	Praha, Hlavni Mesto
France	CHU de Brest -Site Hopital Morvan ( Site 0616)	Brest	Bretagne
France	Hopital Prive Jean Mermoz ( Site 0607)	Lyon	Auvergne
France	Hopital de la Timone ( Site 0617)	Marseille	Bouches-du-Rhone
France	Centre D Oncologie de Gentilly ( Site 0609)	Nancy	Meurthe-et-Moselle
France	Institut de Cancerologie du Gard - CHU Caremeau ( Site 0610)	Nimes	Gard
France	Hopital Tenon ( Site 0612)	Paris
France	Institut de Cancerologie Lucien Neuwirth ( Site 0613)	Saint-Priest-en-Jarez	Loire
France	Centre Paul Strauss ( Site 0615)	Strasbourg	Bas-Rhin
France	Institut Gustave Roussy ( Site 0600)	Villejuif	Val-de-Marne
Germany	Uniklinik RWTH Aachen ( Site 0718)	Aachen	Nordrhein-Westfalen
Germany	Charite Campus Virchow-Klinikum - CVK ( Site 0700)	Berlin
Germany	Gynaekologisches Zentrum ( Site 0712)	Bonn	Nordrhein-Westfalen
Germany	Klinikum Chemnitz gGmbH ( Site 0711)	Chemnitz	Sachsen
Germany	Klinikum Dortmund gGmbH ( Site 0717)	Dortmund	Nordrhein-Westfalen
Germany	Universitaetsklinikum Duesseldorf ( Site 0704)	Duesseldorf	Nordrhein-Westfalen
Germany	Staedtisches Krankenhaus Kiel GmbH ( Site 0709)	Kiel	Schleswig-Holstein
Germany	HELIOS Klinikum Krefeld ( Site 0715)	Krefeld	Nordrhein-Westfalen
Germany	Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0710)	Muenchen	Bayern
Germany	Universitaetsklinikum Muenster ( Site 0720)	Muenster	Nordrhein-Westfalen
Germany	Caritas Klinikum Saarbruecken St. Theresia ( Site 0702)	Saarbruecken	Saarland
Germany	Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0707)	Stuttgart	Baden-Wurttemberg
Hungary	Orszagos Onkologiai Intezet ( Site 0800)	Budapest
Hungary	Uzsoki Utcai Korhaz ( Site 0803)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0801)	Debrecen
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz ( Site 0802)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 0805)	Pecs	Baranya
Israel	Soroka Medical Center ( Site 1006)	Beer-Sheva
Israel	Hillel Yaffe Medical Center ( Site 1011)	Hadera
Israel	Carmel Medical Center ( Site 1007)	Haifa
Israel	Rambam Medical Center ( Site 1002)	Haifa
Israel	Edith Wolfson Medical Center ( Site 1003)	Holon
Israel	Shaare Zedek Medical Center ( Site 1005)	Jerusalem
Israel	Rabin Medical Center ( Site 1004)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 1000)	Ramat Gan
Israel	Sourasky Medical Center ( Site 1001)	Tel Aviv
Italy	IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1108)	Bari	Abruzzo
Italy	Sacro Cuore di Gesu Fatebenefratelli ( Site 1112)	Benevento
Italy	Ospedale Cannizzaro ( Site 1110)	Catania
Italy	ASST Lecco. Ospedale A. Manzoni ( Site 1101)	Lecco
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1115)	Milano
Italy	Istituto Europeo di Oncologia ( Site 1100)	Milano	Lombardia
Italy	A.O.U. Federico II di Napoli ( Site 1107)	Napoli
Italy	Istituto Oncologico Veneto IRCCS ( Site 1113)	Padova	Veneto
Italy	Azienda Ospedaliera Policlinico Umberto I ( Site 1111)	Roma
Italy	Policlinico Universitario Gemelli ( Site 1105)	Roma
Italy	A.O.U. Citta della Salute e della Scienza di Torino ( Site 1104)	Torino	Piemonte
Italy	Presidio Ospedaliero Santa Chiara ( Site 1109)	Trento
Italy	A.O. Univ. S. M. della Misericordia ( Site 1114)	Udine
Japan	Saitama Medical University International Medical Center ( Site 2604)	Hidaka	Saitama
Japan	Kagoshima City Hospital ( Site 2612)	Kagoshima
Japan	National Cancer Center Hospital East ( Site 2602)	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital ( Site 2613)	Kawasaki	Kanagawa
Japan	Saitama Cancer Center ( Site 2614)	Kitaadachi-gun	Saitama
Japan	National Hospital Organization Shikoku Cancer Center ( Site 2601)	Matsuyama	Ehime
Japan	Kyorin University Hospital ( Site 2610)	Mitaka	Tokyo
Japan	University of the Ryukyus Hospital ( Site 2616)	Nakagami-gun	Okinawa
Japan	Niigata Cancer Center Hospital ( Site 2618)	Niigata
Japan	Osaka International Cancer Institute ( Site 2617)	Osaka
Japan	Gunma Prefectural Cancer Center ( Site 2609)	Ota	Gunma
Japan	Hokkaido University Hospital ( Site 2607)	Sapporo	Hokkaido
Japan	Iwate Medical University Hospital ( Site 2606)	Shiwa-gun	Iwate
Japan	National Defense Medical College Hospital ( Site 2608)	Tokorozawa	Saitama
Japan	National Cancer Center Hospital ( Site 2605)	Tokyo
Japan	Ehime University Hospital ( Site 2600)	Toon	Ehime
Korea, Republic of	Seoul National University Bundang Hospital ( Site 2404)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 2402)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 2401)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2403)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2400)	Seoul
Poland	Bialostockie Centrum Onkologii ( Site 1412)	Bialystok	Podlaskie
Poland	Szpitale Pomorskie Sp. z o.o. ( Site 1407)	Gdynia	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1406)	Gliwice	Slaskie
Poland	Swietokrzyskie Centrum Onkologii SPZOZ ( Site 1410)	Kielce	Swietokrzyskie
Poland	Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Russian Federation	Arkhangelsk Clinical Oncological Dispensary ( Site 1508)	Arkhangelsk	Arkhangel Skaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509)	Kazan	Tatarstan, Respublika
Russian Federation	FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1500)	Moscow	Moskva
Russian Federation	FSCC of Special Types of Med. Care and Technologies ( Site 1503)	Moscow	Moskva
Russian Federation	Medical Rehabilitation Center ( Site 1502)	Moscow	Moskva
Russian Federation	A. Tsyb Medical Radiological Research Center ( Site 1513)	Obninsk	Kaluzskaja Oblast
Russian Federation	City Clinical Oncology Center ( Site 1505)	Saint Petersburg	Sankt-Peterburg
Russian Federation	National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1504)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)	Ufa	Baskortostan, Respublika
South Africa	Cancercare ( Site 1706)	Cape Town	Western Cape
South Africa	Groote Schuur Hospital ( Site 1704)	Cape Town	Gauteng
South Africa	The Oncology Centre ( Site 1709)	Durban	Kwazulu-Natal
South Africa	Outeniqua Cancercare Oncology Unit ( Site 1708)	George	Western Cape
South Africa	Wits Clinical Research ( Site 1702)	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials Pty Ltd ( Site 1707)	Kraaifontein	Western Cape
South Africa	Cancer Care Langenhoven Drive Oncology Centre ( Site 1701)	Port Elizabeth	Eastern Cape
South Africa	Curo Oncology ( Site 1710)	Pretoria	Gauteng
South Africa	Department of Medical Oncology ( Site 1703)	Pretoria	Gauteng
South Africa	Little Company of Mary Hospital ( Site 1700)	Pretoria	Gauteng
South Africa	Wilgers Oncology Centre ( Site 1705)	Pretoria	Gauteng
South Africa	Sandton Oncology Medical Group PTY LTD ( Site 1712)	Sandton	Gauteng
Spain	Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 1608)	A Coruna	La Coruna
Spain	Hospital Provincial San Pedro de Alcantara ( Site 1607)	Caceres
Spain	Hospital Universitario de Donostia ( Site 1602)	Donostia	Gipuzkoa
Spain	Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1603)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Lucus Augusti ( Site 1609)	Lugo
Spain	Clinica Universitaria de Navarra ( Site 1600)	Madrid
Spain	Xarxa Assistencial Universitaria Manresa ( Site 1605)	Manresa	Barcelona
Spain	Hospital Universitario Virgen del Rocio ( Site 1604)	Sevilla
Spain	Hospital de Terrassa ( Site 1606)	Terrassa	Barcelona
Spain	Hospital General Universitario de Valencia ( Site 1610)	Valencia	Valenciana, Comunitat
Spain	Instituto Valenciano de Oncologia ( Site 1601)	Valencia	Valenciana, Comunitat
Taiwan	Changhua Christian Hospital ( Site 2507)	Changhua
Taiwan	China Medical University Hospital ( Site 2506)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 2510)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 2508)	Tainan
Taiwan	MacKay Memorial Hospital ( Site 2500)	Taipei
Taiwan	National Taiwan University Hospital ( Site 2502)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 2503)	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital ( Site 2501)	Taoyuan
Turkey	Ankara UTF Cebeci Arastirma ve Uygulama Hastanesi ( Site 1905)	Ankara
Turkey	Etlik Zubeyde Hanim Kadin Hastaliklari Egitim ve Arastirma Hastanesi ( Site 1903)	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi ( Site 1901)	Antalya
Turkey	Uludag Universitesi Tip Fakultesi ( Site 1904)	Bursa
Turkey	Bakirkoy Sadi Konuk Egitim ve Arastirma Hastanesi ( Site 1907)	Istanbul
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1900)	Istanbul
Turkey	Medipol Universite Hastanesi ( Site 1909)	Istanbul
Turkey	Istanbul Acibadem University Atakent Hospital ( Site 1902)	Kucukcekmece	Istanbul
Turkey	Sakarya Universitesi Tip Fakultesi Hastanesi ( Site 1906)	Sakarya
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 2181)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2180)	Kharkiv	Kharkivska Oblast
Ukraine	Municipal non-profit Enterprise Khmelnytskyi Regional Antitu-Gynecological Oncology department, Poli	Khmelnytskyi	Khmelnytska Oblast
Ukraine	Kyiv City Clinical Oncological Center ( Site 2140)	Kyiv
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2170)	Lviv	Lvivska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 2121)	Odesa	Odeska Oblast
Ukraine	RMI - Sumy Regional Clinical Oncology Dispensary ( Site 2191)	Sumy	Sumska Oblast
Ukraine	Central City Clinical Hospital ( Site 2150)	Uzhgorod	Zakarpatska Oblast
United States	Emory School of Medicine ( Site 0053)	Atlanta	Georgia
United States	Weinberg Cancer Institute at Franklin Square ( Site 0035)	Baltimore	Maryland
United States	Texas Oncology, P.A. - Bedford ( Site 8005)	Bedford	Texas
United States	University of Alabama at Birmingham (UAB) ( Site 0036)	Birmingham	Alabama
United States	Disney Family Cancer Center ( Site 0042)	Burbank	California
United States	MD Anderson Cancer Center at Cooper ( Site 0067)	Camden	New Jersey
United States	Miami Valley Hospital [Dayton, OH] ( Site 0073)	Centerville	Ohio
United States	Rush University Medical Center ( Site 0019)	Chicago	Illinois
United States	University of Chicago ( Site 0049)	Chicago	Illinois
United States	Oncology/Hematology Care Clinical Trials, LLC ( Site 8001)	Cincinnati	Ohio
United States	The Bing Cancer Center ( Site 0044)	Columbus	Ohio
United States	Parkland Hospital ( Site 0081)	Dallas	Texas
United States	Texas Oncology-Dallas Presbyterian Hospital ( Site 8004)	Dallas	Texas
United States	UT Southwestern Medical Center ( Site 0046)	Dallas	Texas
United States	Sanford Roger Maris Cancer Center ( Site 0082)	Fargo	North Dakota
United States	Northeast Georgia Medical Center ( Site 0029)	Gainesville	Georgia
United States	Virginia Cancer Specialists, PC ( Site 8003)	Gainesville	Virginia
United States	OSU Wexner Medical Center ( Site 0076)	Hilliard	Ohio
United States	Dr. Sudarshan K. Sharma, LTD ( Site 0061)	Hinsdale	Illinois
United States	Saint Vincent Hospital and Health Center ( Site 0012)	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics ( Site 0005)	Iowa City	Iowa
United States	Saint Dominic - Jackson Memorial Hospital ( Site 0072)	Jackson	Mississippi
United States	Northwell Health- Monter Cancer Center ( Site 0075)	Lake Success	New York
United States	Dartmouth Hitchcock Medical Center ( Site 0024)	Lebanon	New Hampshire
United States	University of Kentucky ( Site 0045)	Lexington	Kentucky
United States	MEDICAL COLLEGE OF WISCONSIN ( Site 0064)	Milwaukee	Wisconsin
United States	Smilow Cancer Center at Yale-New Haven ( Site 0057)	New Haven	Connecticut
United States	Kaiser Permanente Oncology Clinical Trial -Oakland ( Site 0077)	Oakland	California
United States	Nebraska Methodist Hospital ( Site 0063)	Omaha	Nebraska
United States	Women and Infants Hospital [Providence, RI] ( Site 0039)	Providence	Rhode Island
United States	Kaiser Permanente Oncology Clinical Trials-Roseville ( Site 0084)	Roseville	California
United States	Kaiser Permanente Oncology Clinical Trials-Sacramento ( Site 0083)	Sacramento	California
United States	Washington University - School of Medicine ( Site 0062)	Saint Louis	Missouri
United States	Kaiser Permanente Oncology Clinical Trial - San Francisco ( Site 0078)	San Francisco	California
United States	Kaiser Permanente Oncology Clinical Trial - Santa Clara ( Site 0079)	Santa Clara	California
United States	Sarasota Memorial Hospital ( Site 0023)	Sarasota	Florida
United States	Memorial Health University Medical Center ( Site 0011)	Savannah	Georgia
United States	Sanford Gynecology Oncology ( Site 0004)	Sioux Falls	South Dakota
United States	Holy Name Medical Center ( Site 0037)	Teaneck	New Jersey
United States	University of Arizona Cancer Center ( Site 0074)	Tucson	Arizona
United States	Texas Oncology, P.A. Texas Oncology-Tyler ( Site 8006)	Tyler	Texas
United States	Kaiser Permanente N. CA Regional Oncology Clinical Trials ( Site 0008)	Vallejo	California
United States	Kaiser Permanente Oncology Clinical Trial - Walnut Creek ( Site 0080)	Walnut Creek	California

Sponsors (3)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	European Network of Gynaecological Oncological Trial Groups (ENGOT), Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine, 

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 the Investigator in Participants with Programmed Death-Ligand 1 (PD-L1)-Positive Tumors (Combined Positive Score [CPS]=10)	PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. 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 lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be reported for participants with PD-L1-positive (CPS=10) tumors.	Up to approximately 57 months
Primary	PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants	PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. 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 lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be reported for all participants.	Up to approximately 57 months
Secondary	Overall Survival (OS) in All Participants	OS is defined as the time from the date of randomization to death due to any cause. The OS will be reported for all participants.	Up to approximately 6 years
Secondary	OS in Participants with PDL-1 Positive Tumors (CPS = 10)	OS is defined as the time from the date of randomization to death due to any cause. The OS will be reported for all participants with PD-L1 positive tumors (CPS=10).	Up to approximately 6 years
Secondary	PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1-Positive Tumors (CPS=10)	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. 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 lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be reported for participants with PD-L1-positive (CPS=10) tumors.	Up to approximately 57 months
Secondary	PFS Per RECIST 1.1 as Assessed by BICR in All Participants	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. 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 lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be reported for all participants.	Up to approximately 57 months
Secondary	PFS After Second-line Treatment (PFS2) Following Discontinuation of Study Treatment as Assessed by the Investigator in Participants with PD-L1-Positive Tumors (CPS=10)	PFS2 is defined as the time from randomization until PD (clinical or radiological) after second-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for participants with PD-L1-positive (CPS=10) tumors.	Up to approximately 78 months
Secondary	PFS2 Following Discontinuation of Study Treatment as Assessed by the Investigator in All Participants	PFS2 is defined as the time from randomization until PD (clinical or radiological) after second-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for all participants.	Up to approximately 78 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.	Up to approximately 73 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 6 years
Secondary	Mean Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)	Participants are asked to answer 2 questions from the EORTC QLQ-C30 about their GHS: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" Responses are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status. The mean change from baseline in GHS/QoL score of participants will be reported.	Baseline and End of Study Participation (Up to approximately 6 years)
Secondary	Mean Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale	Participants are asked to answer 6 questions from the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28) abdominal/GI symptom scale about abdominal pain, bloated feeling in abdomen/stomach, changes in clothing fit, changes in bowel habit, flatulence and stomach fullness when eating. Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better abdominal/GI symptoms. The mean change from baseline in abdominal/GI symptom score of participants will be reported.	Baseline and End of Study Participation (Up to approximately 6 years)
Secondary	Time to deterioration (TTD) of GHS/QoL score using EORTC QLQ-C30	Participants are asked to answer 2 questions from the EORTC QLQ-C30 about their GHS: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" Responses are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as =10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported.	Up to approximately 6 years
Secondary	Time to deterioration (TTD) of abdominal/GI symptoms using EORTC QLQ-OV28	Participants are asked to answer 6 questions from the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28) abdominal/GI symptom scale about abdominal pain, bloated feeling in abdomen/stomach, changes in clothing fit, changes in bowel habit, flatulence and stomach fullness when eating. Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better abdominal/GI symptoms. TTD is defined as the time from the first EORTC QLQ-OV28 assessment to deterioration (defined as =10-point decrease in EORTC QLQ-OV28 score from baseline) or death, whichever occurs first. The TTD in abdominal/GI symptom score of participants will be reported.	Up to approximately 6 years
Secondary	Time to First Subsequent Anti-cancer Treatment (TFST)	TFST is defined as the time from randomization to initiation of first subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TFST will be reported.	Up to approximately 6 years
Secondary	Time to Second Subsequent Anti-cancer Treatment (TSST)	TSST is defined as the time from randomization to initiation of second subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TSST will be reported.	Up to approximately 6 years
Secondary	Time to Discontinuation of Study Treatment or Death (TDT)	TDT is defined as the time from the date of randomization to discontinuation of study treatment or death due to any cause, whichever occurs first. The TDT will be reported.	Up to approximately 6 years
Secondary	Pathological Complete Response (pCR) Rate	pCR is defined as all surgical specimens collected during the interval debulking surgery are microscopically negative for malignancy. The pCR rate for all surgical specimens will be reported.	Up to approximately 30 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary