A Randomized Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin in Subjects With Unresectable Advanced, Recurrent or Metastatic Previously Untreated Esophageal Squamous Cell Carcinoma
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 970
- Locations
- 190
- Primary Endpoint
- Overall Survival (OS) in Participants With Tumor Cell PD-L1
Study Overview
Brief Summary
The main purpose of this study is to compare how long subjects with esophageal cancer live overall or live without disease progression after receiving nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Must have histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of esophagus
- •Male or Female at least 18 years of age
- •Must have esophageal cancer that cannot be operated on, or treated with definitive chemoradiation with curative intent, that is advanced, reoccurring or has spread out
- •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 which are symptomatic or require treatment
- •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 and/or detectable virus
- •Other protocol defined inclusion/exclusion criteria apply
Arms & Interventions
Nivolumab + Cisplatin + Fluorouacil
Intervention: Cisplatin (Drug)
Nivolumab + Ipilimumab
Intervention: Nivolumab (Biological)
Nivolumab + Ipilimumab
Intervention: Ipilimumab (Biological)
Nivolumab + Cisplatin + Fluorouacil
Intervention: Nivolumab (Biological)
Nivolumab + Cisplatin + Fluorouacil
Intervention: Fluorouracil (Drug)
Cisplatin + Fluorouracil
Intervention: Cisplatin (Drug)
Cisplatin + Fluorouracil
Intervention: Fluorouracil (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS) in Participants With Tumor Cell PD-L1
Time Frame: From the date of randomization to up to the date of death (up to approximately 20 months)
Overall Survival (OS) is defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS will be censored on the last date the subject was known to be alive.
Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1
Time Frame: From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 9 months)
Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented progressive disease (PD) per Blinded Independent Central Review (BICR) or death due to any cause. Participants who die without a reported prior PD per BICR (and die without start of subsequent therapy) will be considered to have progressed on the date of death. Participants who did not have documented PD per BICR per RECIST1.1 criteria and who did not die, will be censored at the date of the last evaluable tumor assessment on or prior to initiation of the subsequent anti-cancer therapy. Participants who did not have any on-study tumor assessments and did not die (or died after initiation of the subsequent anti-cancer therapy) will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported PD per BICR will be censored at the last tumor assessment on or prior to initiation of the subsequent anti-cancer therapy.
Secondary Outcomes
- Overall Survival (OS) in All Randomized Participants(From the date of randomization to up to the date of death (up to approximately 88 months))
- Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR(From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 88 months))
- Objective Response Rate (ORR) as Assessed by BICR(From the date of randomization to up to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (up to 88 months))