A Phase 3 interventional study of Nivolumab and Sorafenib in Hepatocellular Carcinoma, sponsored by Bristol-Myers Squibb. Completed at 138 sites in 22 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-17.
Sponsored by Bristol-Myers Squibb · Phase 3, Interventional, and Treatment
The purpose of this study is to determine if nivolumab or sorafenib is more effective in the treatment of Advanced Hepatocellular Carcinoma.
3,249 studies on the registry are indexed under Carcinoma, Hepatocellular; 974 are open to participants now.
This study's enrollment of 743 is above the median of 55 across 2,347 interventional studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →Bristol-Myers Squibb is the lead sponsor of 1,562 studies on the registry; 118 are open to participants now.
Of its 435 completed or terminated interventional studies of FDA-regulated products, 227 (52%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria apply
Nivolumab specified dose on specified days
Drug: Nivolumab
Sorafenib specified dose on specified days
Drug: Sorafenib
Overall Survival (OS)
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.
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)
Objective Response Rate (ORR) Per BICR RECIST 1.1
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
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)
Progression-Free Survival (PFS)
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.
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)
Efficacy Based on PD-L1 Expression - OS and PFS
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.
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)
Efficacy Based on PD-L1 Expression - ORR
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.
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)
| Milestone | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Started | 371 | 372 |
| Completed | 367 | 363 |
| Not completed | 4 | 9 |
| Withdrew: Participant request to stop therapy | 0 | 2 |
| Withdrew: Participant withdrew consent | 1 | 5 |
| Withdrew: Participant no longer meets criteria | 3 | 2 |
| Milestone | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Started | 367 | 363 |
| Completed | 0 | 0 |
| Not completed | 367 | 363 |
| Withdrew: Disease progression | 263 | 244 |
| Withdrew: Study drug toxicity | 37 | 41 |
| Withdrew: Death | 1 | 1 |
| Withdrew: Adverse event unrelated to study drug | 39 | 41 |
| Withdrew: Participant request to stop treatment | 8 | 18 |
| Withdrew: Participant withdrew consent | 3 | 7 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Maximum clinical benefit | 1 | 0 |
| Withdrew: Poor/non-compliance | 1 | 1 |
| Withdrew: Participant no longer meets criteria | 1 | 0 |
| Withdrew: Other reason | 12 | 8 |
| Withdrew: Not reported | 1 | 0 |
| Withdrew: Administrative reason by sponsor | 0 | 1 |
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.
| Months | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Overall Survival (OS) | 16.39 (13.93 to 18.37) | 14.69 (11.89 to 17.22) |
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
| Percentage of participants | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Objective Response Rate (ORR) Per BICR RECIST 1.1 | 15.4 (11.8 to 19.4) | 7.0 (4.6 to 10.1) |
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.
| Months | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Progression-Free Survival (PFS) | 3.68 (3.06 to 3.88) | 3.75 (3.71 to 4.47) |
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.
| Months | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| >=1%, OS | 16.07 (8.41 to 22.34) | 8.62 (5.72 to 16.30) |
| >=1%, PFS | 3.84 (2.10 to 7.62) | 3.58 (1.97 to 5.36) |
| <1%, OS | 16.72 (13.93 to 18.56) | 15.24 (12.58 to 18.10) |
| <1%, PFS | 3.61 (2.43 to 3.81) | 3.75 (3.71 to 5.32) |
| without PD-L1 quantifiable, OS | 16.23 (5.82 to NA) | 22.05 (1.77 to NA) |
| without PD-L1 quantifiable, PFS | 2.00 (1.87 to NA) | 6.13 (1.08 to 11.17) |
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.
| Percentage of participants | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| >=1%, ORR | 28.2 (18.1 to 40.1) | 9.4 (3.5 to 19.3) |
| <1%, ORR | 12.2 (8.7 to 16.5) | 6.7 (4.1 to 10.1) |
| without PD-L1 quantifiable, ORR | 20.0 (0.5 to 71.6) | 0.0 (0.0 to 36.9) |
Collected over All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nivolumab 240 mg | 321/371 (86.5%) | 216/367 (58.9%) | 339/367 (92.4%) |
| Sorafenib 400 mg | 335/372 (90.1%) | 216/363 (59.5%) | 351/363 (96.7%) |
| Event | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 69/367 | 70/363 |
| General physical health deteriorationGeneral disorders | 8/367 | 14/363 |
| Abdominal painGastrointestinal disorders | 7/367 | 11/363 |
| Hepatic failureHepatobiliary disorders | 10/367 | 7/363 |
| AscitesGastrointestinal disorders | 9/367 | 7/363 |
| Oesophageal varices haemorrhageGastrointestinal disorders | 4/367 | 8/363 |
| AnaemiaBlood and lymphatic system disorders | 8/367 | 6/363 |
| PyrexiaGeneral disorders | 8/367 | 7/363 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 7/367 | 6/363 |
| SepsisInfections and infestations | 7/367 | 2/363 |
| Event | Nivolumab 240 mg | Sorafenib 400 mg |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 100/367 | 191/363 |
| Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders | 29/367 | 181/363 |
| Decreased appetiteMetabolism and nutrition disorders | 77/367 | 135/363 |
| FatigueGeneral disorders | 103/367 | 117/363 |
| PruritusSkin and subcutaneous tissue disorders | 88/367 | 51/363 |
| HypertensionVascular disorders | 33/367 | 85/363 |
| Aspartate aminotransferase increasedInvestigations | 84/367 | 60/363 |
| Abdominal painGastrointestinal disorders | 69/367 | 82/363 |
| RashSkin and subcutaneous tissue disorders | 75/367 | 59/363 |
| AlopeciaSkin and subcutaneous tissue disorders | 6/367 | 71/363 |
| Age, Categorical(Participants) | Nivolumab 240 mg | Sorafenib 400 mg | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 185 | 176 | 361 |
| >=65 years | 186 | 196 | 382 |
| Age, Continuous(years) | Nivolumab 240 mg | Sorafenib 400 mg | Total |
|---|---|---|---|
| Mean | 63.9 ± 10.61 | 64.5 ± 10.91 | 64.2 ± 10.76 |
| Sex: Female, Male(Participants) | Nivolumab 240 mg | Sorafenib 400 mg | Total |
|---|---|---|---|
| Female | 57 | 55 | 112 |
| Male | 314 | 317 | 631 |
| Ethnicity (NIH/OMB)(Participants) | Nivolumab 240 mg | Sorafenib 400 mg | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 10 | 15 |
| Not Hispanic or Latino | 180 | 170 | 350 |
| Unknown or Not Reported | 186 | 192 | 378 |
| Race (NIH/OMB)(Participants) | Nivolumab 240 mg | Sorafenib 400 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 165 | 167 | 332 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 2 | 5 |
| White | 199 | 196 | 395 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 6 | 10 |
Showing the first 100 of 138 sites across 22 countries.
Documents are hosted by the registry — open the source record to download them.
Ran from Dec 2015 to primary completion in May 2019, 41 months.
Results were first posted in Jun 2020, 1 year after primary completion.
Of 47 industry-sponsored phase 3 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 51 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 63. This study's 41 months is below that.
Counting every sponsor, half of 130 studies reached it within 57 months; a quarter within 44 and three quarters within 83.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Nivolumab