Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)

Gastroesophageal Junction Adenocarcinoma Clinical Trial

Official title:

A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03615326
• Other study ID #: 3475-811
• Secondary ID: MK-3475-81118414
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 5, 2018
• Est. completion date: December 30, 2024

Study information

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

Clinical Trial Summary

The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).

Description:

Pembrolizumab (200 mg) or placebo will be administered intravenously [IV] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m^2 5-fluorouracil [5-FU] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m^2 capecitabine administered orally twice daily [BID] on days 1-14 of each 3-week cycle and 130 mg/m^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine [CDHP], and potassium oxonate [Oxo]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m^2) administered IV on Day 1 each 3-week cycle.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 738
• Est. completion date: December 30, 2024
• Est. primary completion date: March 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma
• HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
• Has measurable disease as defined by RECIST 1.1 as determined by the site investigator
• Male participants must agree to use approved contraception
• Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment
• Has a life expectancy of greater than 6 months
• Has adequate organ function

Exclusion Criteria:

• Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
• Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• Has had radiotherapy within 14 days of randomization
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
• Has an active infection requiring systemic therapy
• Has poorly controlled diarrhea
• Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Has peripheral neuropathy > Grade 1
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
• A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
• Has active or clinically significant cardiac disease
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• 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
• Has severe hypersensitivity (=Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
• Has had an allogeneic tissue/solid organ transplant
• 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, Cluster of Differentiation 137 [CD137])

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Gastric Neoplasms
• Gastroesophageal Junction Adenocarcinoma
• Stomach Neoplasms

Intervention

Biological:
• Pembrolizumab
200 mg on Day 1 of each 3-week cycle as an IV infusion.
• Placebo
Solution for IV infusion on Day 1 of each 3-week cycle.

Drug:
• Cisplatin
80 mg/m^2 on Day 1 of each 3-week cycle as an IV infusion, administered as part of FP chemotherapy regimen.
• 5-FU
800 mg/m^2/day continuous on Days 1-5 of each 3-week cycle (120 hours or per local standard), administered as part of FP chemotherapy regimen.
• Oxaliplatin
130 mg/m^2 on Day 1 of each 3-week cycle over 2 hours as an IV infusion, administered as part of CAPOX chemotherapy regimen and as part of SOX chemotherapy regimen.
• Capecitabine
1000 mg/m^2 as oral capsules BID on Days 1-14 of each 3-week cycle, administered as part of CAPOX chemotherapy regimen.
• S-1
Combination product of tegafur, CDHP, and Oxo. Oral capsules BID on Days 1-14 of each 3-week cycle based on body surface area (BSA): <1.25 m^2 BSA =40 mg, 1.25 to <1.5 m^2 BSA=50 mg, =1.5 m^2 BSA=60 mg. Administered as part of SOX chemotherapy regimen.

Biological:
• Trastuzumab
8 mg/kg loading dose and then 6 mg/kg maintenance dose administered IV on day 1 of each 3-week cycle.

Locations

Country	Name	City	State
Australia	Monash Health ( Site 2202)	Clayton	Victoria
Australia	Liverpool Hospital ( Site 2206)	Liverpool	New South Wales
Australia	Westmead Hospital ( Site 2200)	Westmead	New South Wales
Australia	Southern Medical Day Care Centre ( Site 2207)	Wollongong	New South Wales
Brazil	CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0205)	Curitiba	Parana
Brazil	CEPON - Centro de Pesquisas Oncologicas ( Site 0200)	Florianopolis	Santa Catarina
Brazil	Instituto do Cancer do Ceara ( Site 0208)	Fortaleza	Ceara
Brazil	Hospital de Caridade de Ijui ( Site 0202)	Ijui	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceicao ( Site 0203)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0201)	Rio de Janeiro
Brazil	Hospital Sao Rafael ( Site 0209)	Salvador	Bahia
Brazil	IBCC - Instituto Brasileiro de Controle do Cancer ( Site 0204)	Sao Paulo
Chile	Fundacion Arturo Lopez Perez FALP ( Site 0302)	Santiago	Region M. De Santiago
Chile	Instituto Nacional del Cancer ( Site 0303)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 0301)	Santiago	Region M. De Santiago
Chile	Clinica Universidad Catolica del Maule ( Site 0305)	Talca	Maule
Chile	Centro Investigación del Cáncer James Lind ( Site 0300)	Temuco	Araucania
China	Beijing Cancer Hospital ( Site 2413)	Beijing	Beijing
China	Fifth Medical Center of CPLA General Hospital ( Site 2415)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 2419)	Beijing	Beijing
China	The First Hospital Of Jilin University ( Site 2402)	Chang chun	Jilin
China	Xiangya Hospital Central-South University ( Site 2426)	Changsha	Hunan
China	900 Hospital of the Joint ( Site 2420)	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital ( Site 2418)	Fuzhou	Fujian
China	Guangdong General Hospital ( Site 2433)	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital ( Site 2412)	Hangzhou	Zhejiang
China	The First Affiliated Hospital.Zhejiang University ( Site 2408)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 2409)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 2407)	Harbin	Heilongjiang
China	Jiangsu Cancer Hospital ( Site 2432)	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center ( Site 2424)	Shanghai	Shanghai
China	Shanghai General Hospital ( Site 2404)	Shanghai	Anhui
China	Zhongshan Hospital affiliated to Fudan University ( Site 2401)	Shanghai	Shanghai
China	Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2430)	Urumqi	Xinjiang
China	The First Affiliated Hospital of Xiamen University ( Site 2431)	Xiamen	Fujian
China	Henan Cancer Hospital ( Site 2400)	Zhengzhou	Henan
France	Hopital Jean Minjoz Besancon ( Site 0901)	Besancon	Doubs
France	C.H.R.U. de Brest - Hopital Morvan ( Site 0913)	Brest	Finistere
France	Centre Oscar Lambret ( Site 0911)	Lille	Nord
France	Centre Leon Berard ( Site 0904)	Lyon	Rhone
France	CHU Hopital Saint Antoine ( Site 0905)	Paris
France	CHU de Rouen ( Site 0912)	Rouen	Ain
France	Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0902)	Saint-Herblain	Val-de-Marne
France	HUS Hopital Hautepierre ( Site 0910)	Strasbourg	Bas-Rhin
France	Institut Gustave Roussy ( Site 0900)	Villejuif	Val-de-Marne
Germany	Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 1026)	Berlin
Germany	Klinikum Bremen Nord ( Site 1017)	Bremen
Germany	Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 1001)	Dresden	Sachsen
Germany	Asklepios Klinik Altona ( Site 1000)	Hamburg
Germany	Facharztzentrum Eppendorf ( Site 1025)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 1019)	Hannover	Niedersachsen
Germany	SLK-Kliniken Heilbronn ( Site 1015)	Heilbronn	Baden-Wurttemberg
Germany	Universitaetsklinikum Leipzig AOeR ( Site 1007)	Leipzig	Sachsen
Germany	Klinikum Ludwigsburg ( Site 1014)	Ludwigsburg	Baden-Wurttemberg
Germany	Klinikum rechts der Isar der Technischen Universitaet ( Site 1027)	Muenchen	Bayern
Germany	Innere Medizin I, Universitaetsklinikum Tuebingen ( Site 1020)	Tuebingen	Baden-Wurttemberg
Guatemala	Celan SA ( Site 0504)	Guatemala
Guatemala	Grupo Angeles SA ( Site 0501)	Guatemala
Guatemala	Medi-K Cayala ( Site 0505)	Guatemala
Guatemala	Nucare Center ( Site 0506)	Guatemala
Guatemala	Oncomedica ( Site 0500)	Guatemala
Guatemala	Centro Regional de Sub Especialidades Medicas SA ( Site 0502)	Quetzaltenango
Ireland	Beaumont Hospital ( Site 1506)	Dublin
Ireland	Saint James's Hospital ( Site 1505)	Dublin
Ireland	Tallaght University Hospital ( Site 1513)	Dublin
Israel	Soroka University Medical Center ( Site 1603)	Beer Sheva
Israel	Rambam Health Care Campus ( Site 1606)	Haifa
Israel	Edith Wolfson Medical Center ( Site 1605)	Holon
Israel	Hadassah Ein Kerem Medical Center ( Site 1604)	Jerusalem
Israel	Meir Medical Center ( Site 1609)	Kfar-Saba
Israel	Rabin Medical Center ( Site 1602)	Petah Tikva
Israel	Chaim Sheba Medical Center. ( Site 1607)	Ramat Gan
Israel	Sourasky Medical Center ( Site 1601)	Tel Aviv
Italy	Humanitas Gavazzeni ( Site 1106)	Bergamo
Italy	Universita Magna Graecia di Catanzaro ( Site 1107)	Catanzaro
Italy	IEO Istituto Europeo di Oncologia ( Site 1105)	Milano
Italy	Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 1102)	Modena
Italy	A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1103)	Napoli
Italy	Istituto Oncologico Veneto ( Site 1101)	Padova
Italy	Ospedale Civile Spirito Santo ( Site 1104)	Pescara
Italy	AUOP Ospedale Santa Chiara ( Site 1100)	Pisa	Toscana
Japan	Hyogo Cancer Center ( Site 2619)	Akashi	Hyogo
Japan	Chiba Cancer Center ( Site 2623)	Chiba
Japan	National Hospital Organization Kyushu Cancer Center ( Site 2609)	Fukuoka
Japan	Gifu University Hospital ( Site 2621)	Gifu
Japan	Kansai Medical University Hospital ( Site 2618)	Hirakata	Osaka
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 2625)	Hiroshima
Japan	Ibaraki Prefectural Central Hospital ( Site 2611)	Kasama	Ibaraki
Japan	National Cancer Center Hospital East ( Site 2605)	Kashiwa	Chiba
Japan	Kagawa University Hospital ( Site 2604)	Kita-gun	Kagawa
Japan	Saitama Cancer Center ( Site 2620)	Kitaadachi-gun	Saitama
Japan	Kobe City Medical Center General Hospital ( Site 2614)	Kobe	Hyogo
Japan	Kumamoto University Hospital ( Site 2601)	Kumamoto
Japan	National Hospital Organization Shikoku Cancer Center ( Site 2615)	Matsuyama	Ehime
Japan	Kyorin University Hospital ( Site 2608)	Mitaka	Tokyo
Japan	Aichi Cancer Center Hospital ( Site 2617)	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital ( Site 2622)	Niigata
Japan	Gunma Prefectural Cancer Center ( Site 2602)	Ohta	Gunma
Japan	National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26	Osaka
Japan	Osaka General Medical Center ( Site 2624)	Osaka
Japan	Osaka International Cancer Institute ( Site 2613)	Osaka
Japan	Kindai University Hospital ( Site 2616)	Osakasayama	Osaka
Japan	Osaki Citizen Hospital ( Site 2626)	Osaki	Miyagi
Japan	Osaka University Hospital ( Site 2600)	Suita	Osaka
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 2607)	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital ( Site 2612)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 2610)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 2606)	Tokyo
Japan	Toranomon Hospital ( Site 2628)	Tokyo
Japan	Tochigi Cancer Center ( Site 2627)	Utsunomiya	Tochigi
Japan	Kanagawa Cancer Center ( Site 2603)	Yokohama	Kanagawa
Korea, Republic of	Asan Medical Center ( Site 2702)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 2701)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2703)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2700)	Seoul
New Zealand	Auckland City Hospital ( Site 2300)	Auckland
Poland	Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1710)	Bielsko-Biala	Slaskie
Poland	Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1715)	Gdynia	Pomorskie
Poland	Przychodnia Lekarska Komed ( Site 1716)	Konin	Wielkopolskie
Poland	Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1708)	Koscierzyna	Pomorskie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1709)	Lublin	Lubelskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii. ( Site 1712)	Wroclaw	Dolnoslaskie
Poland	Uniwersytecki Szpital Kliniczny im. J. M. Radeckiego we Wroclawiu ( Site 1705)	Wroclaw	Dolnoslaskie
Russian Federation	Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1815)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Blokhin National Medical Oncology ( Site 1805)	Moscow	Moskva
Russian Federation	Podolsky City Clinical Hospital ( Site 1817)	Podolsk	Moskovskaya Oblast
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1801)	Saint Petersburg	Sankt-Peterburg
Russian Federation	St Petersburg City Clinical Oncology Dispensary ( Site 1812)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Leningrad Regional Oncology Center ( Site 1800)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Medical University REAVIZ ( Site 1816)	Samara	Samarskaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1807)	Ufa	Baskortostan, Respublika
Spain	Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1410)	Badalona	Barcelona
Spain	Hospital General Universitari Vall d Hebron ( Site 1401)	Barcelona
Spain	Hospital General Universitario de Elche ( Site 1404)	Elche	Alicante
Spain	Hospital Universitario Ramon y Cajal ( Site 1400)	Madrid
Spain	Hospital Universitario Central de Asturias ( Site 1402)	Oviedo	Asturias
Spain	Hospital Universitario Quiron Madrid ( Site 1407)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Marques de Valdecilla ( Site 1405)	Santander	Cantabria
Turkey	Adana Sehir Hastanesi ( Site 2002)	Adana
Turkey	Abdurrahman Yurtaslan Onkoloji Egitim ve Arastirma Hastanesi ( Site 2006)	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2017)	Ankara
Turkey	Trakya Universitesi Tip Fakultesi ( Site 2015)	Edirne
Turkey	Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2000)	Erzurum
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2001)	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi Hastanesi ( Site 2011)	Izmir
Turkey	Malatya Inonu Universitesi Tip Fakultesi Hastanesi ( Site 2009)	Malatya
Turkey	Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 2012)	Sakarya
Ukraine	City Clinical Hosp.4 of DCC ( Site 2102)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 2105)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 2112)	Kharkiv	Kharkivska Oblast
Ukraine	Medical Center Asklepion LLC ( Site 2115)	Khodosivka	Kyivska Oblast
Ukraine	MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2101)	Kryviy Rih	Dnipropetrovska Oblast
Ukraine	Clinic of National Cancer Institute ( Site 2104)	Kyiv	Kyivska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 2110)	Kyiv
Ukraine	Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2114)	Kyiv	Kyivska Oblast
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2106)	Lviv	Lvivska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 2108)	Odesa	Odeska Oblast
Ukraine	Medical Centre LLC Oncolife ( Site 2103)	Zaporizhzhya	Zaporizka Oblast
United Kingdom	Castle Hill Hospital ( Site 1501)	Cottingham	East Riding Of Yorkshire
United Kingdom	Royal Hospital in Derby ( Site 1514)	Derby	Derbyshire
United Kingdom	Ninewells Hospital and Medical School ( Site 1504)	Dundee	Dundee City
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 1512)	London
United Kingdom	St Georges University Hospitals NHS Foundation Trust. ( Site 1500)	London	London, City Of
United Kingdom	University College London Hospital NHS Foundation Trust ( Site 1508)	London	London, City Of
United Kingdom	The Christie Hospital NHS Foundation Trust ( Site 1503)	Manchester
United Kingdom	Mount Vernon Cancer Centre ( Site 1507)	Northwood
United Kingdom	Royal Marsden Hospital ( Site 1510)	Sutton	Surrey
United Kingdom	Manor Hospital Walsall England ( Site 1515)	Walsall
United States	Beth Israel Deaconess Medical Center ( Site 0070)	Boston	Massachusetts
United States	Dana-Farber Cancer Institute [Boston, MA] ( Site 0010)	Boston	Massachusetts
United States	Levine Cancer Institute ( Site 0015)	Charlotte	North Carolina
United States	Duke Cancer Institute ( Site 0042)	Durham	North Carolina
United States	Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0065)	Harrison	New York
United States	University of Texas MD Anderson Cancer Center ( Site 0001)	Houston	Texas
United States	UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0045)	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center - Plantation ( Site 0026)	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0071)	Middletown	New Jersey
United States	Minnesota Oncology Hematology, PA ( Site 8001)	Minneapolis	Minnesota
United States	Pacific Cancer Care ( Site 0063)	Monterey	California
United States	Memorial Sloan-Kettering Cancer Center ( Site 0017)	New York	New York
United States	Southeastern Regional Medical Center, Inc. ( Site 0058)	Newnan	Georgia
United States	UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0050)	Orange	California
United States	Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0025)	Philadelphia	Pennsylvania
United States	Allegheny General Hospital ( Site 0053)	Pittsburgh	Pennsylvania
United States	Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 8000)	Roanoke	Virginia
United States	University of Rochester ( Site 0041)	Rochester	New York
United States	Washington University School of Medicine ( Site 0040)	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance ( Site 0038)	Seattle	Washington
United States	Sanford Hematology Oncology-Sioux Falls SD ( Site 0004)	Sioux Falls	South Dakota
United States	CTCA Southwestern ( Site 0060)	Tulsa	Oklahoma
United States	Midwestern Regional Medical Center, Inc. ( Site 0059)	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  China,  France,  Germany,  Guatemala,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Russian Federation,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) per RECIST 1.1 assessed by BICR	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered progression. PFS will be determined for each treatment arm.	Up to approximately 4 years
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause. OS will be determined for each treatment arm.	Up to approximately 5 years
Secondary	Objective Response Rate (ORR) per RECIST 1.1 assessed by BICR	ORR is defined as the percentage of participants who have a Complete Response ([CR], disappearance of all evidence of disease) or Partial Response ([PR], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by BICR. ORR will be determined for each treatment arm.	Up to approximately 5 years
Secondary	Duration of Response (DOR) per RECIST 1.1 assessed by BICR	For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR will be determined for each treatment arm.	Up to approximately 5 years
Secondary	Adverse Events (AE)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experience an AE will be reported for each treatment arm.	Up to approximately 5 years
Secondary	Treatment Discontinuations Due to AEs	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinue study treatment due to an AE will be reported for each treatment arm.	Up to approximately 5 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary