Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer

Gastric Cancer Clinical Trial

— CheckMate649  

Official title:

A Randomized, Multicenter, Open-Label, Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab in Combination With Oxaliplatin Plus Fluoropyrimidine Versus Oxaliplatin Plus Fluoropyrimidine in Subjects With Previously Untreated Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02872116
• Other study ID #: CA209-649
• Secondary ID: 2016-001018-76
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 12, 2016
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to compare how long patients with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2031
• Est. completion date: May 31, 2024
• Est. primary completion date: May 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or Female at least 18 years of age

• Must have gastric cancer or gastroesophageal junction cancer that cannot be operated on and that is advanced or has spread out

• Did not receive neoadjuvant or adjuvant treatment (chemotherapy, radiotherapy, or both) for their disease within the last 6 months

• Must have full activity or, if limited, must be able to walk and carry out light activities such as light house work or office work

• Must agree to provide tumor tissue sample, either from a previous surgery or biopsy within 6 months or fresh, prior to the start of treatment in this study

Exclusion Criteria:

• Presence of tumor cells in the brain or spinal cord that have not been treated

• Active known or suspected autoimmune disease

• Any serious or uncontrolled medical disorder or active infection

• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

• Any positive test result for hepatitis B or C indicating acute or chronic infection

Other protocol-defined inclusion/exclusion criteria apply

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Gastric Cancer
• Gastroesophageal Junction Cancer

Intervention

Drug:
• Nivolumab
Specified dose on specified days
• Ipilimumab
Specified dose on specified days
• Oxaliplatin
Specified dose on specified days
• Capecitabine
Specified dose on specified days
• Leucovorin
Specified dose on specified days
• Fluorouracil
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0030	Caba	Buenos Aires
Argentina	Local Institution - 0028	Capital Federal	Buenos Aires
Argentina	Local Institution - 0029	Capital Federal	Buenos Aires
Argentina	Local Institution - 0027	Cordoba
Argentina	Local Institution - 0184	La Rioja
Argentina	Local Institution - 0026	San Miguel De Tucuman	Tucuman
Argentina	Local Institution - 0183	Viedma	RIO Negro
Australia	Local Institution - 0101	Adelaide	South Australia
Australia	Local Institution - 0103	Ballarat	Victoria
Australia	Local Institution - 0202	Blacktown	New South Wales
Australia	Local Institution - 0100	Gosford	New South Wales
Australia	Local Institution - 0099	Perth	Western Australia
Australia	Local Institution - 0102	Shepparton	Victoria
Australia	Local Institution - 0190	Southport	Queensland
Australia	Local Institution - 0214	St Albans	Victoria
Brazil	Local Institution - 0048	Barretos	Sao Paulo
Brazil	Local Institution - 0046	Ijui	RIO Grande DO SUL
Brazil	Local Institution - 0047	Porto Alegre	RIO Grande DO SUL
Brazil	Local Institution - 0053	Salvador	Bahia
Brazil	Local Institution - 0054	Sao Paulo
Canada	Local Institution - 0035	Edmonton	Alberta
Canada	Local Institution - 0036	London	Ontario
Canada	Local Institution - 0052	Montreal	Quebec
Canada	Local Institution - 0196	Montreal	Quebec
Canada	Local Institution - 0051	Quebec City	Quebec
Canada	Local Institution - 0068	Sherbrooke	Quebec
Canada	Local Institution - 0067	Toronto	Ontario
Canada	Local Institution - 0034	Trois-Rivieres	Quebec
Chile	Local Institution - 0058	Independencia	Santiago
Chile	Local Institution - 0031	Santiago	Metropolitana
Chile	Local Institution - 0057	Santiago	Metropolitana
Chile	Local Institution - 0032	Temuco	Araucania
Chile	Local Institution - 0033	Vina Del Mar	Valparaiso
China	Local Institution - 0171	Beijing	Beijing
China	Local Institution - 0176	Beijing	Beijing
China	Local Institution - 0178	Beijing	Beijing
China	Local Institution - 0155	Changchun	Jilin
China	Local Institution - 0156	Changchun	Jilin
China	Local Institution - 0173	Changsha	Hunan
China	Local Institution - 0158	Changzhou	Jiangsu
China	Local Institution - 0185	Fuzhou	Fujian
China	Local Institution - 0166	Guangzhou	Guangdong
China	Local Institution - 0161	Hangzhou	Zhejiang
China	Local Institution - 0168	Hangzhou	Zhejiang
China	Local Institution - 0174	Hangzhou
China	Local Institution - 0160	Harbin	Heilongjiang
China	Local Institution - 0154	Nanjing	Jiangsu
China	Local Institution - 0187	Nanjing	Jiangsu
China	Local Institution - 0182	Qingdao	Shandong
China	Local Institution - 0165	Shanghai	Shanghai
China	Local Institution - 0175	Shanghai	Shanghai
China	Local Institution - 0181	Shenyang	Liaoning
China	Local Institution - 0172	Tianjin
China	Local Institution - 0167	Urumqi	Xinjiang
China	Local Institution - 0159	Zhengzhou	Henan
Colombia	Local Institution - 0022	Bogota
Colombia	Local Institution - 0025	Bogota	Cundinamarca
Colombia	Local Institution - 0024	Pasto
Czechia	Local Institution - 0197	Brno
Czechia	Local Institution - 0200	Brno
France	Local Institution - 0080	Caen
France	Local Institution - 0081	Dijon
France	Local Institution - 0077	Lille
France	Local Institution - 0083	Montpellier
France	Local Institution - 0113	Nantes
France	Local Institution - 0079	Nice Cedex 2
France	Local Institution - 0078	Paris
France	Local Institution - 0119	Plérin
Germany	Local Institution - 0094	Berlin
Germany	Local Institution - 0095	Cologne
Germany	Local Institution - 0089	Dresden
Germany	Local Institution - 0188	Dusseldorf
Germany	Local Institution - 0091	Essen
Germany	Local Institution - 0096	Freiburg
Germany	Local Institution - 0093	Hamburg
Germany	Local Institution - 0092	Mainz	Rheinland-Pfalz
Germany	Local Institution - 0149	Muenchen
Greece	Local Institution - 0056	Athens
Greece	Local Institution - 0019	Ioannina
Greece	Local Institution - 0017	Nea Kifissia	Attikí
Greece	Local Institution - 0018	Patras
Hong Kong	Local Institution - 0191	Hong Kong
Hong Kong	Local Institution - 0195	Hong Kong
Hungary	Local Institution - 0007	Budapest
Hungary	Local Institution - 0008	Budapest
Hungary	Local Institution - 0108	Debrecen
Israel	Local Institution - 0118	Haifa
Israel	Local Institution - 0116	Jerusalem
Israel	Local Institution - 0115	Petach Tikva
Israel	Local Institution - 0117	Ramat-gan
Israel	Local Institution - 0114	Tel Aviv
Italy	Local Institution - 0062	Bergamo
Italy	Local Institution - 0205	Modena
Italy	Local Institution - 0061	Napoli
Italy	Local Institution - 0063	Pisa
Italy	Local Institution - 0059	Roma
Italy	Local Institution - 0064	San Giovanni Rotondo
Japan	Local Institution - 0128	Chiba-shi	Chiba
Japan	Local Institution - 0126	Chuo-ku	Tokyo
Japan	Local Institution - 0125	Kashiwa	Chiba
Japan	Local Institution - 0127	Kita-Gun	Kagawa
Japan	Local Institution - 0123	Kitaadachi-gun	Saitama
Japan	Local Institution - 0122	Minato-ku	Tokyo
Japan	Local Institution - 0130	Nagoya	Aichi
Japan	Local Institution - 0137	Sapporo-shi	Hokkaido
Japan	Local Institution - 0124	Suita-shi	Osaka
Japan	Local Institution - 0129	Tokyo
Korea, Republic of	Local Institution - 0131	Seoul
Korea, Republic of	Local Institution - 0132	Seoul
Mexico	Local Institution - 0215	Mexico City	Distrito Federal
Mexico	Local Institution - 0216	Queretaro
Mexico	Local Institution - 0217	Toluca	Estado DE Mexico
Peru	Local Institution - 0037	Lima
Peru	Local Institution - 0039	Lima
Peru	Local Institution - 0139	Lima
Peru	Local Institution - 0189	Lima
Poland	Local Institution - 0016	Lublin
Poland	Local Institution - 0013	Tarnobrzeg
Poland	Local Institution - 0014	Warszawa
Portugal	Local Institution - 0043	Lisboa
Portugal	Local Institution - 0210	Porto
Romania	Local Institution - 0012	Baia Mare	Jud Maramures
Romania	Local Institution - 0040	Bucharest
Romania	Local Institution - 0042	Cluj-Napoca
Romania	Local Institution - 0041	Craiova	Dolj
Romania	Local Institution - 0055	Suceava
Russian Federation	Local Institution - 0071	Chelyabinsk
Russian Federation	Local Institution - 0069	Moscow
Russian Federation	Local Institution - 0086	Moscow
Russian Federation	Local Institution - 0105	Moscow
Russian Federation	Local Institution - 0085	St. Petersburg
Singapore	Local Institution - 0193	Singapore	Central Singapore
Singapore	Local Institution - 0194	Singapore
Spain	Local Institution - 0050	Badajoz
Spain	Local Institution - 0209	Badalona-barcelona
Spain	Local Institution - 0044	Barcelona
Spain	Local Institution - 0049	Pozuelo De Alarcon, Madrid
Spain	Local Institution - 0045	Valencia
Spain	Local Institution - 0212	Zaragoza
Taiwan	Local Institution - 0148	Tainan
Taiwan	Local Institution - 0133	Taipei
Taiwan	Local Institution - 0134	Taoyuan County
Turkey	Local Institution - 0203	Ankara
Turkey	Local Institution - 0211	Ankara
Turkey	Local Institution - 0201	Antalya
Turkey	Local Institution - 0208	Diyarbakir
Turkey	Local Institution - 0207	Edrine
United Kingdom	Local Institution - 0074	London	Greater London
United Kingdom	Local Institution - 0073	Manchester	Greater Manchester
United Kingdom	Local Institution - 0076	Nottingham	Nottinghamshire
United Kingdom	Local Institution - 0072	Southampton
United Kingdom	Local Institution - 0075	Sutton	Surrey
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Local Institution - 0219	Arlington Heights	Illinois
United States	Local Institution - 0066	Aurora	Colorado
United States	Local Institution - 0021	Baltimore	Maryland
United States	Local Institution - 0140	Bedford	Texas
United States	Local Institution - 0002	Boston	Massachusetts
United States	Local Institution - 0135	Boston	Massachusetts
United States	Local Institution - 0120	Chicago	Illinois
United States	Local Institution - 0138	Cleveland	Ohio
United States	Local Institution - 0186	Cleveland	Ohio
United States	Local Institution - 0143	Dallas	Texas
United States	Local Institution - 0213	Dallas	Texas
United States	Local Institution - 0151	Denver	Colorado
United States	Local Institution - 0146	Eugene	Oregon
United States	Florida Cancer Specialists S.	Fort Myers	Florida
United States	Local Institution - 0004	Houston	Texas
United States	Local Institution - 0005	Los Angeles	California
United States	Local Institution - 0179	Marietta	Georgia
United States	Local Institution - 0147	Miami	Florida
United States	Local Institution - 0104	Nashville	Tennessee
United States	Local Institution - 0003	New York	New York
United States	Local Institution - 0150	Newport News	Virginia
United States	Local Institution - 0065	Pittsburgh	Pennsylvania
United States	Texas Oncology-Plano East	Plano	Texas
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	California Pacific Medical Center Research Institute	San Francisco	California
United States	Local Institution - 0136	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS = 5	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS (combined positive score) = 5. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From the date of randomization up to the date of death, up to approximately 17 months
Primary	Progression Free Survival (PFS) in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy With PD-L1 CPS = 5	Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS = 5. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
Secondary	OS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy with PD-L1 CPS = 1, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From the date of randomization up to the date of death, up to approximately 17 months
Secondary	PFS in Participants Treated With Nivolumab Plus Chemotherapy vs Chemotherapy	Progression free survival (PFS), defined as the time from randomization to the date of the first documented progressive disease (PD) or death due to any cause, in participants treated with Nivolumab plus Chemotherapy vs Chemotherapy by BICR per RECIST1.1 in participants with PD-L1 CPS = 10, 1, or all randomized subjects. Progreessive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 10 months)
Secondary	Objective Response Rate	Objective response rate (ORR) as assessed by BICR in participants with PD-L1 CPS = 10, 5, 1, or all randomized participants. ORR is a percentage of participants determined by the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of measurable participants with target lesion at baseline. BOR is defined as the best response designation as determined by the BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1 as determined by the BICR) or the date of subsequent anti-cancer therapy, whichever occurs first. CR is defined as the disappearance of all target lesions. PR is define as at 30% decrease in the sum of diameters of target lesions. The 806 chemotherapy treated participants are split into two separate arms (Arm 2a and Arm 2b) to act as comparison groups to the other treatment arms.	From randomization to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 43 months)
Secondary	OS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy	Overall survival (OS), defined as the time from randomization to the time of death, in participants treated with Nivolumab plus Ipilimumab vs Chemotherapy with PD-L1 CPS (combined positive score) = 1, 5, 10, and all randomized participants. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From the date of randomization up to the date of death, up to approximately 14 months
Secondary	Time to Symptom Deterioration (TTSD)	TTSD is defined as the the time from randomization until a clinically meaningful decline from baseline in Gastric Cancer Subscale (GaCS) score. A clinically meaningful deterioration is defined as a reduction of 8.2 points in the GaCS score. Subjects who do not deteriorate will be censored at the time of their last GACS assessment. Subjects without baseline GaCS assessment will be censored on the randomization date. Those with baseline GaCS, who do not have any GaCS assessments after randomization will be censored on the day after randomization.	From randomization until a clinically meaningful decline from baseline in GaCS score
Secondary	PFS in Participants Treated With Nivolumab Plus Ipilimumab vs Chemotherapy	Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented PD or death due to any cause. PD is determined by blinded independent committee review (BICR) per RECIST1.1 criteria in participants treated with Nivolumab plus Ipilumab vs Chemotherapy with PD-L1 CPS = 10, 5, 1 or all randomized participants. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking in reference the smallest sum on study that also demonstrated an absolute increase of at least 5 mm. CPS is defined as the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.	From randomization to the date of the first documented progressive disease (PD) per BICR or death due to any cause (up to approximately 9 months)

External Links

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