Study to compare how long subjects with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2016-001018-76-PL
• Date of registration: 23/08/2016
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb International Corporation
• Public title: Study to compare how long subjects with gastric or gastroesophageal junction cancer live after receiving nivolumab and ipilimumab or nivolumab and chemotherapy compared with patients receiving chemotherapy alone
• Scientific 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 (CheckMate 649: CHECKpoint pathway and nivoluMab clinical Trial Evaluation 649) - CheckMate 649
• Date of first enrolment: 19/10/2016
• Target sample size: 3200
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001018-76
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
a) All subjects must have inoperable, advanced, locally advanced or metastatic GC or GEJ or distal esophageal carcinoma and have histologically confirmed predominant adenocarcinoma.
b) Subject must be previously untreated with systemic treatment including HER 2 inhibitors given as primary therapy for advanced or metastatic disease.
c) Allowed Prior Therapies: Prior adjuvant or neoadjuvant chemotherapy, radiotherapy and/or chemoradiotherapy for GC or GEJ cancer are permitted as long as the last administration of the prior
regimen (whichever was given last) occurred at least 6 months prior to randomization. Palliative
radiotherapy is allowed and must be completed 2 weeks prior to randomization.
d) Subject must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST 1.1 criteria.
e) ECOG performance status score of 0 or 1.
f) Tumor tissue must be provided for PD-L1 biomarker analyses prior to randomization.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 960

Exclusion criteria:
a) Known Her2 positive status
b) Subjects with untreated CNS metastases.
c) Subjects with ascites which cannot be controlled with appropriate interventions.
d) Subjects with > Grade 1 peripheral neuropathy.
e) Treatment with botanical preparations (eg herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 2 weeks prior to randomization/treatment.
f) Participants who have received a live/attenuated vaccine within 30 days of first treatment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Gastric or Gastroesophageal Junction Cancer
MedDRA version: 20.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: LLT Classification code 10056267 Term: Gastroesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Opdivo (100mg/10 ml)
Product Name: NIVOLUMAB - 10ml vial- CLINICAL
Product Code: BMS-936558
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Current Sponsor code: BMS-936558-01
Other descriptive name: BMS936558, MDX1106, ONO-4538
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: IPILIMUMAB
Product Code: BMS-734016
Pharmaceutical Form: Solution for injection
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016
Other descriptive name: BMS734016
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Oxaliplatin Kabi
Product Name: Oxaliplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Oxaliplatin Bendalis
Product Name: Oxaliplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Capecitabine Accord
Product Name: Capecitabine Accord
Pharmaceutical Form: F

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: a) 52.4 months after first patient randomized
b) 28.2 months after first patient randomized

Main Objective: Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine:
-To compare OS in subjects with advanced or metastatic GC or GEJ cancer with PD-L1 CPS >=5
-To compare PFS, as assessed by BICR in subjects with advanced or metastatic GC or GEJ cancer with PD-L1 CPS >=5 in PFS population (PFS population defined in Section 8.2)

Primary end point(s): Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine:
a) Overall survival (OS) of Nivolumab + oxaliplatin plus fluoropyrimidine vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS =5
b) Progression-free Survival (PFS) as assessed by BICR of Nivolumab + oxaliplatin plus fluoropyrimidine vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS =5 in PFS population

Secondary Objective: Nivolumab plus ipilimumab vs oxaliplatin plus fluoropyrimidine:
- compare OS in subjects with PD-L1 CPS = 5, = 1 or all randomized subjects
- evaluate OS in subjects with PD-L1 CPS = 10
- evaluate PFS, as assessed by BICR, in subjects with PD-L1 CPS = 10, 5, 1 or all randomized subjects
- evaluate ORR, as assessed by BICR, in subjects with PD-L1 CPS =10, 5, 1 or all randomized subjects
- compare the TTSD as assessed using the GaCS of the FACT-Ga in subjects with PD-L1 CPS = 5 or all randomized subjects

Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine:
- compare OS in subjects with PD-L1 CPS = 1 or all randomized subjects
- evaluate OS in subjects with PD-L1 CPS = 10
- evaluate PFS, as assessed by BICR, in subjects with PD-L1 CPS =10, 1 or all randomized subjects in PFS population
- evaluate ORR, as assessed by BICR, in subjects with PD-L1 CPS =10, 5, 1, or all randomized subjects

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: a, b, c, d, e) 52.4 months after first patient randomized
f, g) 52.4 months after first patient randomized
h, i) 28.2 months after first patient randomized

Secondary end point(s): Nivolumab plus ipilimumab vs oxaliplatin plus fluoropyrimidine:
a) OS of Nivolumab + ipilimumab vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS = 5, 1, or all randomized subjects
b) OS of Nivolumab + ipilimumab vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS = 10
c) PFS, as assessed by BICR, of Nivolumab + ipilimumab vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS =10, 5, 1 or all randomized subjects
d) Objective Response Rate (ORR), as assessed by BICR, of Nivolumab + ipilimumab vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS = 10, 5, 1 or all randomized subjects
e) Time to symptom deterioration (TTSD) of Nivolumab + ipilimumab vs oxaliplatin + fluoropyrimidine in participants with PD-L1 CPS = 5 or all randomized subjects

Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine:
f) OS of Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine in participants with PD-L1 CPS = 1 or all randomized subjects
g) OS of Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus Fluoropyrimidine in participants with PD-L1 CPS=10
h) PFS, as assessed by BICR, for Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus Fluoropyrimidine in participants with PD-L1 CPS =10, 1 or all randomized subjects in PFS population
i) ORR, as assessed by BICR, Nivolumab in combination with oxaliplatin plus fluoropyrimidine vs oxaliplatin plus fluoropyrimidine in participants with PD-L1 CPS =10, 5, 1, or all randomized subjects

Secondary ID(s)

CA209-649

2016-001018-76-ES

NCT02872116

Source(s) of Monetary Support

Bristol-Myers Squibb International Corporation

Ethics review

Status: Approved
Approval date:
Contact: