A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459)
ClinicalTrials.gov processed this data on March 15, 2024. Link to the current ClinicalTrials.gov record.Recruitment Status
COMPLETED - HAS RESULTS(See Contacts and Locations)
Verified March 2024 by Bristol-Myers Squibb, Ono Pharmaceutical Co. Ltd
Sponsor
Bristol-Myers SquibbInformation Provided by (Responsible Party)
Bristol-Myers SquibbClinicaltrials.gov Identifier
NCT02576509Other Study ID Numbers: CA209-459
First Submitted: October 13, 2015
First Posted: October 15, 2015
Results First Posted: June 26, 2020
Last Update Posted: March 19, 2024
Last Verified: March 2024
History of Changes
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Study Description
Not Provided| Condition or Disease | Intervention/Treatment |
|---|---|
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Study Design
| Study Type | Interventional |
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| Actual Enrollment | 743 participants |
| Design Allocation | Randomized |
| Interventional Model | Parallel Assignment |
| Masking | None (Open Label) |
| Primary Purpose | Treatment |
| Official Title | A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459) |
| Study Start Date | December 7, 2015 |
| Actual Primary Completion Date | May 30, 2019 |
| Actual Study Completion Date | February 7, 2024 |
Groups and Cohorts
| Group/ Cohort | Intervention/ Treatment |
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Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)] OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates.
Based on Kaplan-Meier Estimates.
Secondary Outcome Measures
- Objective Response Rate (ORR) Per BICR RECIST 1.1 [the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)] ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later.
Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors - Progression-Free Survival (PFS) [time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)] PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.
- Efficacy Based on PD-L1 Expression - OS and PFS [the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)] PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:
Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.
Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).
PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:
PD-L1 > X %: ≥ X % PD-L1 expression
PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.
Confidence interval based on the Clopper and Pearson method. - Efficacy Based on PD-L1 Expression - ORR [the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)] PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as:
Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling.
Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate).
PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression:
PD-L1 > X %: ≥ X % PD-L1 expression
PD-L1 < X %: < X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored.
Confidence interval based on the Clopper and Pearson method.
Eligibility Criteria
| Ages Eligible for Study | 18 Years and Older (Adult, Older Adult) |
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| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | No |
| Inclusion Criteria |
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| Exclusion Criteria |
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Contacts and Locations
| Sponsors and Collaborators | Bristol-Myers Squibb, Ono Pharmaceutical Co. Ltd |
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| Ono Pharmaceutical Co. Ltd | |
| Locations |
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| Investigators |
Study Documents (Full Text)
- Documents Provided by Bristol-Myers Squibb: Study Protocol January 15, 2019
- Documents Provided by Bristol-Myers Squibb: Statistical Analysis Plan July 2, 2018
More Information
Additional Information
Publications
Additional Relevant MeSH Terms
- Carcinoma
- Carcinoma, Hepatocellular
- Neoplasms, Glandular and Epithelial
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Liver Neoplasms
- Digestive System Neoplasms
- Neoplasms by Site
- Digestive System Diseases
- Liver Diseases