A Study to Evaluate Efficacy in Subjects with Esophageal Cancer Treated with Nivolumab and Ipilimumab or Nivolumab Combined with Fluorouracil plus Cisplatin versus Fluorouracil plus Cisplatin

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 - CheckMate 648

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-001514-20-CZ

Enrollment

1127

Registered

2016-10-17

Start date

2017-06-06

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Inoperable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC). MedDRA version: 20.0 Level: LLT Classification code 10055476 Term: Esophageal squamous cell carcinoma System Organ Class: 100000004864

Interventions

Trade Name: Opdivo Product Name: Nivolumab-10 ml vial- CLINICAL Product Code: BMS-936558 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: NIVOLUMAB CAS Number: 946414-94

Eligibility

Sex/Gender

All

Inclusion criteria

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 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 451 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 676

Exclusion criteria

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.

Design outcomes

Primary

Measure	Time frame
Main Objective: 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.;Secondary Objective: - To compare the overall survival (OS) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) in all randomized subjects. - To compare the Progression Free Survival (PFS) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a Blinded Independent Central Review (BICR) in all randomized subjects. - To compare the objective response rate (ORR) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a BICR in subjects with PD-L1 expression 1%. - To compare the ORR of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a BICR in all randomized subjects.;Primary end point(s): - Overall survival (OS) in subjects with PD-L1 expressing tumors. - Progression-free Survival (PFS) (as 1 assessed by blinded independent central review committee {BICR)) in subjects with PD-L1 expressing tumors.;Timepoint(s) of evaluation of this end point: - Overall survival (OS) in subjects with PD-L1 expressing tumors -- approximately 49 months from time first patient is randomized - Progression-free Survival (PFS) (as 1 assessed by blinded independent central review committee (BICR)) in subjects with PD-L1 expressing tumors -- approximately 33 months from time first patient is randomized	—

Measure

Time frame

Main Objective: 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.;Secondary Objective: - To compare the overall survival (OS) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) in all randomized subjects. - To compare the Progression Free Survival (PFS) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a Blinded Independent Central Review (BICR) in all randomized subjects. - To compare the objective response rate (ORR) of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a BICR in subjects with PD-L1 expression 1%. - To compare the ORR of nivolumab plus ipilimumab (Arm A) and nivolumab combined with fluorouracil plus cisplatin (Arm B) to fluorouracil and cisplatin combination (Arm C) as assessed by a BICR in all randomized subjects.;Primary end point(s): - Overall survival (OS) in subjects with PD-L1 expressing tumors. - Progression-free Survival (PFS) (as 1 assessed by blinded independent central review committee {BICR)) in subjects with PD-L1 expressing tumors.;Timepoint(s) of evaluation of this end point: - Overall survival (OS) in subjects with PD-L1 expressing tumors -- approximately 49 months from time first patient is randomized - Progression-free Survival (PFS) (as 1 assessed by blinded independent central review committee (BICR)) in subjects with PD-L1 expressing tumors -- approximately 33 months from time first patient is randomized

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Secondary

Measure	Time frame
Secondary end point(s): - Overall survival (OS) in All Randomized subjects - Progression-free Survival (PFS) (as assessed by BICR) in All Randomized Subjects - Objective Response Rate (ORR) (as assessed by BICR) in subjects with PD-L1 expressing tumors and All Randomized subjects;Timepoint(s) of evaluation of this end point: - Overall survival (OS) in All Randomized subjects -- approximately 49 months from time first patient is randomized - Progression-free Survival (PFS) (as assessed by BICR) in All Randomized Subjects -- approximately 33 months from time first patient is randomized - Objective Response Rate (ORR) (as assessed by BICR) in subjects with PD-L1 expressing tumors and All Randomized subjects -- -- approximately 33 months from time first patient is randomized	—

Measure

Time frame

Secondary end point(s): - Overall survival (OS) in All Randomized subjects - Progression-free Survival (PFS) (as assessed by BICR) in All Randomized Subjects - Objective Response Rate (ORR) (as assessed by BICR) in subjects with PD-L1 expressing tumors and All Randomized subjects;Timepoint(s) of evaluation of this end point: - Overall survival (OS) in All Randomized subjects -- approximately 49 months from time first patient is randomized - Progression-free Survival (PFS) (as assessed by BICR) in All Randomized Subjects -- approximately 33 months from time first patient is randomized - Objective Response Rate (ORR) (as assessed by BICR) in subjects with PD-L1 expressing tumors and All Randomized subjects -- -- approximately 33 months from time first patient is randomized

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Countries

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

Contacts

Public ContactHead of the GCT-SU

Bristol-Myers Squibb International Corporation

clinical.trials@bms.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026