Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001)

Endometrial Neoplasms Clinical Trial

— LEAP-001  

Official title:

A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03884101
• Other study ID #: 7902-001
• Secondary ID: MK-7902-001ENGOT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 11, 2019
• Est. completion date: January 15, 2025

Study information

• Verified date: June 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 compare the efficacy of pembrolizumab + lenvatinib to chemotherapy in female participants with Stage III, IV, or recurrent endometrial carcinoma. It is hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR). It is also hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for overall survival (OS).

As of Amendment 7 eligible participants on study completion will be able to transition to an extension study, if available, in which they can continue to receive pembrolizumab monotherapy, lenvatinib monotherapy, or a combination of both pembrolizumab and lenvatinib as received in the parent study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 842
• Est. completion date: January 15, 2025
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or nonmeasurable but radiographically apparent, per RECIST 1.1 as assessed by BICR (note: may have received prior chemotherapy only if administered concurrently with radiation; may have received prior radiation without concurrent chemotherapy; may have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued =1 week prior to randomization; and may have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy)

• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion that was not previously irradiated, for determination of mismatch repair (MMR) status

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to the first dose of study intervention

• Is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to use contraception during the study and for =120 days after pembrolizumab, =30 days after lenvatinib, or =180 days after (chemotherapy) [if a WOCBP, a pregnancy test will be required within 24 hours of first dose of study drug]

• Has adequately controlled blood pressure within 7 days prior to randomization

• Has adequate organ function based on assessment within 7 days prior to the first dose of study intervention

Exclusion Criteria:

• Has carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas

• Has a central nervous system (CNS) metastasis, unless local therapy (e.g., whole brain radiation therapy, surgery, or radiosurgery) has been completed and have discontinued use of corticosteroids for this indication for =4 weeks prior to starting study medication (major surgery within 3 weeks of the first dose of study drug will be exclusionary)

• Has a known additional malignancy (other than endometrial carcinoma) that is progressing or has required active treatment in the last 3 years

• Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib

• Has a pre-existing Grade =3 gastrointestinal or nongastrointestinal fistula

• Has radiographic evidence of major blood vessel invasion/infiltration

• Has active hemoptysis (bright red blood at =0.5 teaspoon) within 3 weeks prior to the first dose of study intervention or tumor bleeding within 2 weeks prior to randomization

• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction or cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability

• Has any infection requiring systemic treatment

• Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization

• Has a known history of human immunodeficiency virus (HIV) infection (HIV test is required at screening)

• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) [defined as HCV ribonucleic acid (RNA) is detected] (hepatitis B and C testing is required at screening only when mandated by local health authority)

• Has a history of (noninfectious) pneumonitis that required treatment with steroids, or has current pneumonitis

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing 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 (with the exception of psoriasis) that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)

• Has received prior systemic chemotherapy in any setting for the treatment of endometrial carcinoma (note: prior chemotherapy administered concurrently with radiation is permitted)

• Has received prior radiotherapy within 4 weeks prior to randomization (participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis - a 2-week washout is permitted for palliative radiation to non-CNS disease and vaginal brachytherapy)

• Has received prior hormonal therapy for the treatment of endometrial carcinoma within 1 week of randomization

• Has received prior therapy with any treatment targeting vascular endothelial growth factor (VEGF)-directed angiogenesis, an anti-programmed cell death (PD)-1, anti-PD ligand (L)1, or anti-PD L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)

• Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention

• Has known intolerance to study intervention (or any of the excipients)

• Has had an allogenic tissue/solid organ transplant

• 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

Related Conditions & MeSH terms

• Endometrial Neoplasms

Intervention

Drug:
• Lenvatinib
Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.

Biological:
• Pembrolizumab
Pembrolizumab 200 mg IV infusion given on Day 1 of each cycle.

Drug:
• Paclitaxel
Paclitaxel 175 mg/m^2 IV infusion given on Day 1 of each cycle.
• Carboplatin
Carboplatin 10 mg/mL IV infusion at a total dose of are-under-the-curve (AUC) 6 (per Calvert's formula) given on Day 1 of each cycle.

Locations

Country	Name	City	State
Argentina	Hospital Aleman ( Site 2600)	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires ( Site 2603)	Buenos Aires
Argentina	IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2607)	Caba	Buenos Aires
Argentina	Hospital Italiano de La Plata ( Site 2601)	La Plata	Buenos Aires
Argentina	Centro Oncologico Riojano Integral ( Site 2605)	La Rioja
Argentina	Instituto de Investigaciones Clinicas Mar del Plata ( Site 2606)	Mar del Plata	Buenos Aires
Australia	Chris OBrien Lifehouse ( Site 1605)	Camperdown	New South Wales
Australia	Monash Health ( Site 1606)	Clayton	Victoria
Australia	Epworth Freemasons Hospital ( Site 1609)	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital ( Site 1604)	Nedlands	Western Australia
Australia	Prince of Wales Hospital [Australia] ( Site 1603)	Randwick	New South Wales
Australia	Mater Misericordiae Ltd ( Site 1608)	South Brisbane	Queensland
Australia	Royal North Shore Hospital ( Site 1600)	St Leonards	New South Wales
Australia	The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 1602)	Westmead	New South Wales
Austria	Universitatsklinik fuer Frauenheilkunde und Geburtshilfe ( Site 3301)	Graz	Steiermark
Austria	Medizinische Universitat Innsbruck ( Site 3302)	Innsbruck	Tirol
Austria	Medizinische Universitat Wien ( Site 3300)	Vienna	Wien
Belgium	Cliniques Universitaires Saint-Luc ( Site 3203)	Brussels	Bruxelles-Capitale, Region De
Belgium	UZA University Hospital Antwerp ( Site 3204)	Edegem	Antwerpen
Belgium	AZ Maria Middelares Gent ( Site 3202)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 3200)	Leuven	Antwerpen
Belgium	AZ Delta ( Site 3206)	Roeselare	West-Vlaanderen
Brazil	Faculdade de Medicina da Universidade Federal de Minas Gerais ( Site 2708)	Belo Horizonte	Minas Gerais
Brazil	Instituto do Cancer do Ceara ( Site 2703)	Fortaleza	Ceara
Brazil	Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 2702)	Goiania	Goias
Brazil	Hospital de Caridade de Ijui ( Site 2712)	Ijui	Rio Grande Do Sul
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 2701)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional do Cancer II ( Site 2707)	Rio de Janeiro
Brazil	Hospital de Base de Sao Jose de Rio Preto ( Site 2704)	Sao Jose do Rio Preto	Sao Paulo
Brazil	A.C. Camargo Cancer Center ( Site 2705)	Sao Paulo
Brazil	Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 2706)	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 2713)	Sao Paulo
Canada	Cross Cancer Institute ( Site 0408)	Edmonton	Alberta
Canada	Juravinski Cancer Centre ( Site 0406)	Hamilton	Ontario
Canada	BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0402)	Kelowna	British Columbia
Canada	Kingston Health Sciences Centre ( Site 0401)	Kingston	Ontario
Canada	The Credit Valley Hospital ( Site 0403)	Mississauga	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0411)	Montreal	Quebec
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0414)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0404)	Montreal	Quebec
Canada	CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0417)	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0409)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0410)	Toronto	Ontario
Canada	BC Cancer-Vancouver Center ( Site 0412)	Vancouver	British Columbia
China	Beijing Cancer Hospital ( Site 2504)	Beijing	Beijing
China	Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 2501)	Beijing	Beijing
China	Xiangya Hospital Central-South University ( Site 2512)	Changsha	Hunan
China	Chongqing Cancer Hospital ( Site 2513)	Chongqing	Chongqing
China	The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)	Guangzhou	Guangdong
China	Women s Hospital School of Medicine Zhejiang University ( Site 2511)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 2506)	Hangzhou	Zhejiang
China	Anhui Provincial Cancer Hospital ( Site 2509)	Hefei	Anhui
China	Nanjing Maternity and Child Health Care Hospital ( Site 2508)	Nanjing	Jiangsu
China	Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center ( Site 2500)	Shanghai	Shanghai
China	Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)	Shanghai	Shanghai
China	The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)	Urumqi	Xinjiang
China	Hubei Cancer Hospital ( Site 2510)	Wuhan	Hubei
China	The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)	XI An	Shaanxi
Germany	Charite Universitaetsmedizin Berlin ( Site 0609)	Berlin
Germany	Universitaetsklinikum Essen ( Site 0616)	Essen	Nordrhein-Westfalen
Germany	Universitaetsklinikum Jena ( Site 0612)	Jena	Thuringen
Germany	Universitaetsmedizin Mannheim. Klinik fuer Kinder und Jugendmedizin ( Site 0622)	Mannheim	Baden-Wurttemberg
Germany	Universitaetsklinikum Muenster ( Site 0615)	Muenster	Baden-Wurttemberg
Germany	Caritas-Krankenhaus St. Josef Regensburg ( Site 0613)	Regensburg	Bayern
Germany	HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 0623)	Wiesbaden	Hessen
Ireland	Cork University Hospital ( Site 1400)	Cork
Ireland	St James Hospital ( Site 1401)	Dublin
Israel	Rambam Medical Center ( Site 0700)	Haifa
Israel	Edith Wolfson Medical Center ( Site 0703)	Holon	Tell Abib
Israel	Meir Medical Center ( Site 0702)	Kfar-Saba	Central
Israel	Chaim Sheba Medical Center ( Site 0707)	Ramat Gan
Italy	Medical Oncology Ospedale San Donato ( Site 0812)	Arezzo
Italy	IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0801)	Bari
Italy	Ospedale Policlinico S. Orsola-Malpighi ( Site 0803)	Bologna
Italy	Ospedale Antonio Perrino ( Site 0806)	Brindisi
Italy	Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0807)	Catania
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 0800)	Meldola	Emilia-Romagna
Italy	Ospedale dell Angelo ( Site 0810)	Mestre	Venezia
Italy	Istituto Nazionale Tumori Fondazione Pascale ( Site 0808)	Napoli
Italy	Policlinico Universitario Agostino Gemelli ( Site 0805)	Rome	Roma
Japan	Hyogo Cancer Center ( Site 2414)	Akashi	Hyogo
Japan	National Hospital Organization Kyushu Cancer Center ( Site 2405)	Fukuoka
Japan	Saitama Medical University International Medical Center ( Site 2410)	Hidaka	Saitama
Japan	Nippon Medical School Musashi Kosugi Hospital ( Site 2417)	Kawasaki	Kanagawa
Japan	St. Marianna University School of Medicine Hospital ( Site 2416)	Kawasaki	Kanagawa
Japan	Saitama Cancer Center ( Site 2406)	Kitaadachi-gun	Saitama
Japan	Kurume University Hospital ( Site 2403)	Kurume	Fukuoka
Japan	Kyorin University Hospital ( Site 2402)	Mitaka	Tokyo
Japan	University of the Ryukyus Hospital ( Site 2412)	Nakagami-gun	Okinawa
Japan	Niigata Cancer Center Hospital ( Site 2415)	Niigata
Japan	Osaka International Cancer Institute ( Site 2409)	Osaka
Japan	Gunma Prefectural Cancer Center ( Site 2404)	Ota	Gunma
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 2408)	Sapporo	Hokkaido
Japan	National Defense Medical College Hospital ( Site 2418)	Tokorozawa	Saitama
Japan	Keio University Hospital ( Site 2411)	Tokyo
Japan	Showa University Hospital ( Site 2419)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 2401)	Tokyo
Japan	Ehime University Hospital ( Site 2413)	Toon	Ehime
Korea, Republic of	Seoul National University Bundang Hospital ( Site 1802)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 1800)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1803)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1801)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 1804)	Seoul
Mexico	Centro Estatal de Cancerologia de Chihuahua ( Site 3101)	Chihuahua
Mexico	Consultorio Dentro de la Torre Medica Dalinde Oncologia Medica ( Site 3108)	Ciudad de Mexico
Mexico	Centro de Investigacion Clinica Gramel ( Site 3107)	Mexico City
Mexico	Centro Oncologico Internacional. SEDNA ( Site 3106)	Mexico City
Mexico	I CAN Oncology SA de SV ( Site 3102)	Monterrey	Nuevo Leon
Mexico	Hospital San Lucas Cardiologica del Sureste ( Site 3103)	Tuxtla Gutierrez	Chiapas
Poland	Bialostockie Centrum Onkologii ( Site 1005)	Bialystok	Podlaskie
Poland	Centrum Onkologii Instytut im. MSC Oddzial w Gliwicach ( Site 1017)	Gliwice	Slaskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 1019)	Krakow	Malopolskie
Poland	Instytut Centrum Zdrowia Matki Polki ( Site 1020)	Lodz	Lodzkie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1008)	Lublin	Dolnoslaskie
Poland	Wielkopolskie Centrum Onkologii im.M.Sklodowskiej-Curie ( Site 1004)	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1009)	Warsaw	Mazowieckie
Poland	Szpital Kliniczny im Ks Anny Mazowieckiej ( Site 1011)	Warszawa	Mazowieckie
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1108)	Kazan	Tatarstan, Respublika
Russian Federation	Krasnoyarsk Regional Clinical oncology dispensary ( Site 1118)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	FSBI-FRCC of Special Types Med. Care and Technologies FMBA of Russia ( Site 1102)	Moscow	Moskva
Russian Federation	Medical Rehabilitation Center ( Site 1101)	Moscow	Moskva
Russian Federation	Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1100)	Moscow	Moskva
Russian Federation	SPb SBHI City Clinical Oncological Dispensary ( Site 1104)	Saint Petersburg	Sankt-Peterburg
Russian Federation	St.Petersburg Clinical Hospital RAS ( Site 1124)	Saint Petersburg	Sankt-Peterburg
Russian Federation	National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1103)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Railway Hospital of OJSC ( Site 1122)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Samara Regional Clinical Oncology Center ( Site 1117)	Samara	Samarskaya Oblast
Russian Federation	Siberian State Medical University ( Site 1121)	Tomsk	Tomskaya Oblast
Spain	Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 1202)	A Coruna	La Coruna
Spain	Institut Catala d Oncologia Badalona ( Site 1201)	Badalona	Barcelona
Spain	Parc de Salut Mar ( Site 1200)	Barcelona
Spain	Hospital Universitario Reina Sofia ( Site 1207)	Cordoba
Spain	Hospital Clinico San Carlos ( Site 1209)	Madrid
Spain	Hospital Materno Infantil [Malaga, Spain] ( Site 1208)	Malaga
Spain	Hospital General Universitario de Valencia ( Site 1203)	Valencia	Valenciana, Comunitat
Spain	Instituto Valenciano de Oncologia - IVO ( Site 1205)	Valencia	Valenciana, Comunitat
Taiwan	China Medical University Hospital ( Site 1903)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 1902)	Taichung
Taiwan	National Taiwan University Hospital ( Site 1904)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 1900)	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital ( Site 1901)	Taoyuan
Turkey	Baskent Universitesi Adana Uygulama ve Arastirma Hastanesi ( Site 1303)	Adana
Turkey	Cukurova Uni. Tip Fakultesi ( Site 1302)	Adana
Turkey	Baskent Universitesi Ankara Hastanesi ( Site 1300)	Ankara
Turkey	Gazi Universitesi Tip Fakultesi ( Site 1308)	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi ( Site 1301)	Antalya
Turkey	Uludag Universitesi Tip Fakultesi ( Site 1307)	Bursa
Ukraine	City Clinical Hosp.4 of DCC ( Site 1501)	Dnipro	Dnipropetrovska Oblast
Ukraine	Clinical oncology dispensary of Dnipro ( Site 1512)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 1503)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 1509)	Kharkiv	Kharkivska Oblast
Ukraine	Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 1511)	Kharkiv	Kharkivska Oblast
Ukraine	Khmelnitskiy Regional Onkology Dispensary ( Site 1513)	Khmelnitskiy	Khmelnytska Oblast
Ukraine	Medical Center Asklepion LLC ( Site 1514)	Khodosivka	Kyivska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 1505)	Kyiv
Ukraine	Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 1507)	Kyiv	Kyivska Oblast
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 1510)	Kyiv	Kyivska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 1504)	Odesa	Odeska Oblast
United Kingdom	Western General Hospital ( Site 1411)	Edinburgh	Edinburgh, City Of
United Kingdom	UCLH NHS Foundation Trust ( Site 1405)	London	London, City Of
United Kingdom	The James Cook University Hospital ( Site 1403)	Middlesbrough
United Kingdom	Northern Centre for Cancer Care ( Site 1408)	Newcastle Upon Tyne
United Kingdom	Mount Vernon Cancer Centre ( Site 1409)	Northwood	London, City Of
United Kingdom	Churchill Hospital ( Site 1406)	Oxford	Oxfordshire
United States	Georgia Cancer Center at Augusta University ( Site 0222)	Augusta	Georgia
United States	University of Colorado Cancer Center ( Site 0204)	Aurora	Colorado
United States	Memorial Sloan-Kettering Cancer Center At Basking Ridge ( Site 0268)	Basking Ridge	New Jersey
United States	University of North Carolina- Chapel Hill ( Site 0254)	Chapel Hill	North Carolina
United States	Memorial Sloan-Kettering Cancer Center at Commack ( Site 0267)	Commack	New York
United States	Women's Cancer Care ( Site 0208)	Covington	Louisiana
United States	Parkland Health & Hospital System ( Site 0272)	Dallas	Texas
United States	University of Texas Southwestern Medical Center ( Site 0264)	Dallas	Texas
United States	Willamette Valley Cancer Institute and Research Center ( Site 8004)	Eugene	Oregon
United States	Roger Maris Cancer Center ( Site 0277)	Fargo	North Dakota
United States	John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0226)	Hackensack	New Jersey
United States	Memorial Sloan Kettering Cancer Center - West Harrison ( Site 0274)	Harrison	New York
United States	UCLA Hematology and Oncology Clinic (Westwood) ( Site 0233)	Los Angeles	California
United States	University of Miami Health System ( Site 0249)	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0273)	Middletown	New Jersey
United States	Minnesota Oncology Hematology, PA ( Site 8003)	Minneapolis	Minnesota
United States	University of South Alabama, Mitchell Cancer Institute ( Site 0245)	Mobile	Alabama
United States	MSKCC-Bergen ( Site 0276)	Montvale	New Jersey
United States	Smilow Cancer Hospital at Yale New Haven ( Site 0202)	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center ( Site 0246)	New York	New York
United States	The Blavatnik Family- Chelsea Medical Center at Mount Sinai ( Site 0206)	New York	New York
United States	University of Rochester ( Site 0238)	Rochester	New York
United States	Maine Medical Partners ( Site 0217)	Scarborough	Maine
United States	Sanford Cancer Center Oncology Clinic ( Site 0205)	Sioux Falls	South Dakota
United States	Holy Name Medical Center ( Site 0235)	Teaneck	New Jersey
United States	Texas Oncology-The Woodlands ( Site 8000)	The Woodlands	Texas
United States	Arizona Oncology Associates PC- HOPE ( Site 8005)	Tucson	Arizona
United States	Memorial Sloan Kettering Cancer Center - Nassau ( Site 0275)	Uniondale	New York
United States	Legacy Salmon Creek Medical Center ( Site 0253)	Vancouver	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR)	Progression-free survival based on RECIST 1.1 as assessed by BICR. Progression-free survival is measured from the time of randomization to the first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately 31 months
Primary	Overall Survival (OS)	Overall survival is measured from the time of randomization up to death due to any cause.	Up to approximately 45 months
Secondary	Objective response rate (ORR ) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent review (BICR)	The ORR (either confirmed complete response [CR] or partial response [PR]) based on RECIST 1.1 and assessed by BICR will be determined in mismatch repair proficient (pMMR) participants and in all-comer participants who have measurable disease at study entry.	Up to approximately 31 months
Secondary	Mean change from baseline in the global health status/quality of life score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) in pMMR and in all-comer participants	The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. It contains 30 questions (items), 24 of which aggregate into nine multi-item scales representing various aspects, or dimensions, of quality of life (QoL): one global scale, five functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea, pain), and six additional single-symptom items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Individual items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation; a higher score on the global and functional scales represents a higher ("better") level of functioning, and a higher score on the symptom scale represents a higher ("worse") level of symptoms.	Baseline and designated time points up to 27 months
Secondary	Percentage of participants experiencing an adverse event (AE)	An AE is 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.	Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary	Percentage of participants experiencing a serious adverse event (SAE)	An SAE is an AE that results in death, is life-threatening, requires or prolongs hospitalization, results in persistent or significant disability, is a congenital birth defect, or is another important medical event.	Up to approximately 28 months (through 120 days after the last dose of study treatment)
Secondary	Percentage of participants experiencing an immune-related AE (irAE)	Immune-related AEs will be monitored in both arms.	Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary	Percentage of participants discontinuing from study treatment due to an AE(s)	Discontinuations related to AEs will be monitored in both arms.	Up to approximately 24 months (through the last dose of study treatment)

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary