TriangleNCT03143153 · CITED IN SOURCE DOCUMENTS
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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2026-02-17
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
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Survival (OS) in Participants With Tumor Cell PD-L1
Progression-free Survival (PFS) as Assessed by BICR in Participants With Tumor Cell PD-L1
Overall Survival (OS) in All Randomized Participants
Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR
Objective Response Rate (ORR) as Assessed by BICR
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Biological: Nivolumab
- Biological: Ipilimumab
- label
- Nivolumab + Ipilimumab
- type
- EXPERIMENTAL
- intervention Names
- Biological: Nivolumab
- Drug: Cisplatin
- Drug: Fluorouracil
- label
- Nivolumab + Cisplatin + Fluorouacil
- type
- EXPERIMENTAL
- intervention Names
- Drug: Cisplatin
- Drug: Fluorouracil
- label
- Cisplatin + Fluorouracil
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Nivolumab + Cisplatin + Fluorouacil
- Nivolumab + Ipilimumab
- description
- Specified dose on specified days
- name
- Nivolumab
- other Names
- BMS-936558 (Nivolumab)
- Opdivo (Nivolumab)
- type
- BIOLOGICAL
- arm Group Labels
- Nivolumab + Ipilimumab
- description
- Specified dose on specified days
- name
- Ipilimumab
- other Names
- BMS-734016 (Ipilimumab)
- Yervoy (Ipilimumab)
- type
- BIOLOGICAL
- arm Group Labels
- Cisplatin + Fluorouracil
- Nivolumab + Cisplatin + Fluorouacil
- description
- Specified dose on specified days
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Cisplatin + Fluorouracil
- Nivolumab + Cisplatin + Fluorouacil
- description
- Specified dose on specified days
- name
- Fluorouracil
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 970
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- secondary Outcomes
- description
- 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.
- measure
- Overall Survival (OS) in All Randomized Participants
- time Frame
- From the date of randomization to up to the date of death (up to approximately 88 months)
- description
- 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.
- measure
- Progression-free Survival (PFS) in All Randomized Participants as Assessed by BICR
- time Frame
- From the date of randomization to up to the date of the first documented disease progression or death (up to approximately 88 months)
- description
- Objective response rate (ORR) is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation as determined by BICR, recorded between the date of randomization and the date of objectively documented progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Complete response is defined as the disappearance of all target lesions and the reduction of any pathological lymph nodes to \<10 mm.
- measure
- Objective Response Rate (ORR) as Assessed by BICR
- time Frame
- 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)
Full study description
- 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
Source references
- references
- citation
- Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.
- pmid
- 37139963
- type
- DERIVED
- citation
- Kato K, Doki Y, Ogata T, Motoyama S, Kawakami H, Ueno M, Kojima T, Shirakawa Y, Okada M, Ishihara R, Kubota Y, Amaya-Chanaga C, Chen T, Matsumura Y, Kitagawa Y. First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50). Esophagus. 2023 Apr;20(2):291-301. doi: 10.1007/s10388-022-00970-1. Epub 2022 Nov 19.
- pmid
- 36401133
- type
- DERIVED
- citation
- Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y; CheckMate 648 Trial Investigators. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.
- pmid
- 35108470
- type
- DERIVED
- see Also Links
- label
- BMS Clinical Trial Information
- label
- BMS Clinical Trial Patient Recruiting
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-38180332aacaf756f68c
- requested nct id
- NCT03143153
- primary nct id
- NCT03143153
- source kind
- fda_spl_label
- source record id
- 72755838-4a55-4245-949e-16cea13f2584
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- payload sha256
- 913721e08c44fd593791a0d93d34fd8a88bd56715aaad53afbf1f1d5e2ed638a
- payload
- application numbers
- BLA125377
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-38180332aacaf756f68c
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03143153
- occurrences
- context exact
- tellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer Treatment of MSI-H or dMMR mCRC In Combination with Nivolumab CHECKMATE-8HW (NCT03143153) was a randomized, 3-arm, open-label trial in immunotherapy-naive patients across all lines of therapy with unresectable or metastatic CRC with known tumor MSI
- end
- 14656
- exact text
- NCT03143153
- start
- 14645
- context exact
- median OS of 16.9 months in the YERVOY and nivolumab arm and 8.8 months in the chemotherapy arm. yervoy-os-checkmate-743 14.8 Esophageal Cancer CHECKMATE-648 (NCT03143153) was a randomized, active-controlled, open-label trial in patients with previously untreated unresectable advanced, recurrent or metastatic ESCC (squamous or a
- end
- 43620
- exact text
- NCT03143153
- start
- 43609
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00400.json
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- source json pointer
- /results/51/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 72755838-4a55-4245-949e-16cea13f2584
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 658a921a002e81a6b55202efcb78091c2f2526215217a47cb445aaf003f3b7ac
- spl effective time
- 20260820
- spl set id
- 2265ef30-253e-11df-8a39-0800200c9a66
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-6859c0b2f6696ee6b3cd
- requested nct id
- NCT03143153
- primary nct id
- NCT03143153
- source kind
- fda_spl_label
- source record id
- 1ce25608-1b8f-4d49-9ffd-6c8c61bf4f1a
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- payload sha256
- 85f8fbcc2c1aae597c6e89ef468e3f5cd1eedce902b41b156a14be67bd6fb0f7
- payload
- application numbers
- BLA761381
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-6859c0b2f6696ee6b3cd
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03143153
- occurrences
- context exact
- of OPDIVO QVANTIG for this indication is supported by evidence from an adequate and well-controlled study conducted with intravenous nivolumab (CHECKMATE-8HW, NCT03143153), and additional pharmacokinetic and safety data that demonstrated comparable pharmacokinetics and safety profiles between OPDIVO QVANTIG and intravenous nivol
- end
- 71258
- exact text
- NCT03143153
- start
- 71247
- context exact
- s a description of the efficacy results of the adequate and well-controlled study of intravenous nivolumab in this CRC population. CHECKMATE-8HW CHECKMATE-8HW (NCT03143153) was a randomized, 3-arm, open-label trial in immunotherapy-naive patients across all lines of therapy with unresectable or metastatic CRC with known tumor MSI
- end
- 71667
- exact text
- NCT03143153
- start
- 71656
- context exact
- results of the adequate and well-controlled study of intravenous nivolumab in this esophageal squamous cell carcinoma population. CHECKMATE-648 CHECKMATE-648 (NCT03143153) was a randomized, active-controlled, open-label trial in patients with previously untreated unresectable advanced, recurrent or metastatic ESCC (squamous or a
- end
- 99120
- exact text
- NCT03143153
- start
- 99109
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00000.json
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- source json pointer
- /results/99/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 1ce25608-1b8f-4d49-9ffd-6c8c61bf4f1a
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 5bf2986a82b5a92531e13372f09d8e1a224755d4292be776af9561e28041e8bb
- spl effective time
- 20260512
- spl set id
- 7f8c38fa-42f4-4387-9e8c-7a1c66855d8b
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-d848fd837b0d76dccb7d
- requested nct id
- NCT03143153
- primary nct id
- NCT03143153
- source kind
- fda_spl_label
- source record id
- 1fce9e6a-6a7c-4fc0-a3a4-a0099f7bd2ce
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- payload sha256
- 04cea3eb7e35978c3bf3d8b12c64b4136476a03f21e902bfe7b6ef663b351d25
- payload
- application numbers
- BLA125554
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-d848fd837b0d76dccb7d
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03143153
- occurrences
- context exact
- ellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer Treatment of MSI-H or dMMR mCRC In Combination with Ipilimumab CHECKMATE-8HW (NCT03143153) was a randomized, 3-arm, open-label trial in immunotherapy-naive patients across all lines of therapy with unresectable or metastatic CRC with known tumor MSI
- end
- 79239
- exact text
- NCT03143153
- start
- 79228
- context exact
- al - CHECKMATE-577 opdivo-dfs-checkmate-577.jpg First-line Treatment of Unresectable Advanced or Metastatic ESCC Whose Tumors Express PD-L1 (≥1) CHECKMATE-648 (NCT03143153) was a randomized, active-controlled, open-label trial in patients with previously untreated unresectable advanced, recurrent or metastatic ESCC (squamous or a
- end
- 101819
- exact text
- NCT03143153
- start
- 101808
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00100.json
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- source json pointer
- /results/9/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 1fce9e6a-6a7c-4fc0-a3a4-a0099f7bd2ce
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 47f974766bb01dbde354e28e5e29eb6c7328d3adabf94e5593a5044bca4bc462
- spl effective time
- 20260812
- spl set id
- f570b9c4-6846-4de2-abfa-4d0a4ae4e394
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-ed147ac66887ebe1fb98
- requested nct id
- NCT03143153
- primary nct id
- NCT03143153
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- ae34307bb691d47c46a65f222a59b130903b0bb6f81f74d86efa8d978235c117
- payload sha256
- 02cc541ebeb58fc6f89fde010e45d4659f201a4d93440c46855254e36119ddc1
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-ed147ac66887ebe1fb98
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03143153
- occurrences
- context exact
- and chemoimmunotherapy for patients with squamous cell carcinoma):</p> <div class="pdq-content-list"><ol id="_535"><li>In the <a href="/clinicaltrials/NCT03143153">CheckMate 648</a> trial (NCT03143153), 970 adults with previously untreated, unresectable advanced, recurrent, or metastatic squamous cell carcinoma were enro
- end
- 178066
- exact text
- NCT03143153
- start
- 178055
- context exact
- ith squamous cell carcinoma):</p> <div class="pdq-content-list"><ol id="_535"><li>In the <a href="/clinicaltrials/NCT03143153">CheckMate 648</a> trial (NCT03143153), 970 adults with previously untreated, unresectable advanced, recurrent, or metastatic squamous cell carcinoma were enrolled, regardless of tumor cell PD-L1 e
- end
- 178104
- exact text
- NCT03143153
- start
- 178093
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/18487e92114483e1e7.html
- source file sha256
- ae34307bb691d47c46a65f222a59b130903b0bb6f81f74d86efa8d978235c117
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:21:40.423603+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- a637b94429a42b90c83abf50e8a31e75014f7c2723832c386417963ac519dbcf
- source title
- Esophageal Cancer Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: March 21, 2025
- datetime
- 2025-03-21T12:00:00Z
- display
- March 21, 2025
Preserved source evidence · Not medical advice