An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma
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| ClinicalTrials.gov Identifier: NCT02576509 |
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Recruitment Status :
Active, not recruiting
First Posted : October 15, 2015
Results First Posted : June 26, 2020
Last Update Posted : October 13, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatocellular Carcinoma | Drug: Nivolumab Drug: Sorafenib | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 743 participants |
| Allocation: | Randomized |
| Intervention 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) |
| Actual Study Start Date : | December 7, 2015 |
| Actual Primary Completion Date : | May 30, 2019 |
| Estimated Study Completion Date : | June 30, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nivolumab
Nivolumab specified dose on specified days
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Drug: Nivolumab
Specified Dose on Specified Days |
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Active Comparator: Sorafenib
Sorafenib specified dose on specified days
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Drug: Sorafenib
Specified Dose on Specified Days |
- Overall Survival (OS) [ Time Frame: 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.
- Objective Response Rate (ORR) Per BICR RECIST 1.1 [ Time Frame: 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 Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
- Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan
- Child-Pugh Class A
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Exclusion Criteria:
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Prior liver transplant
- Active, known, or suspected autoimmune disease
Other protocol-defined inclusion/exclusion criteria apply
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576509
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| Study Director: | Bristol Myers Squibb | Bristol-Myers Squibb |
Documents provided by Bristol-Myers Squibb:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT02576509 |
| Other Study ID Numbers: |
CA209-459 |
| First Posted: | October 15, 2015 Key Record Dates |
| Results First Posted: | June 26, 2020 |
| Last Update Posted: | October 13, 2022 |
| Last Verified: | October 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 Nivolumab Sorafenib Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Protein Kinase Inhibitors Enzyme Inhibitors |