Phase 2
N=657
An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer
Hepatocellular Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT01658878 ↗Enrolled (actual)
657
Serious AEs
65.1%
Results posted
Dec 2025
Primary outcome: Primary: Number of Participants With Adverse Events (AEs) — 1; 3; 3; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Nivolumab (Biological); Sorafenib (Drug); Ipilimumab (Drug); Cabozantinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bristol-Myers Squibb
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
1; 3; 3; 3; 13; 3 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) |
0; 1; 2; 0; 5; 0 | — |
| PRIMARY Number of Participants With Adverse Events Leading to Discontinuation |
0; 0; 0; 1; 1; 0 | — |
| PRIMARY Number of Participants Who Died |
1; 3; 2; 2; 13; 1 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Specific Liver Tests |
0; 1; 1; 1; 7; 2 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests |
0; 1; 1; 1; 5; 1 | — |
| PRIMARY Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) for Cohort 2 |
19.6; 14.0; 20.0; 13.7 | — |
| PRIMARY Objective Response Rate (ORR) by Investigator for Cohorts 3, 4, 5, and 6 |
11.5; 4.5; 36.0; 26.5; 28.6; 12.2 | — |
| SECONDARY Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) for Cohort 1 |
13.0; 20.0; 13.3 | — |
| SECONDARY Number of Participants With Complete Response (CR) Assessed by Blinded Independent Central Review (BICR) |
1; 0; 0; 2; 0; 2 | — |
| SECONDARY Disease Control Rate (DCR) Assessed by Blinded Independent Central Review (BICR) |
47.8; 70.0; 40.0; 66.1; 56.1; 54.0 | — |
| SECONDARY Duration of Response (DOR) Assessed by Blinded Independent Central Review (BICR) |
NA; 12.55; 6.41; 22.57; 11.30; NA | — |
| SECONDARY Time to Response (TTR) Assessed by Blinded Independent Central Review (BICR) |
1.41; 3.15; 1.99; 2.73; 3.63; 2.78 | — |
| SECONDARY Time to Progression (TTP) Assessed by Blinded Independent Central Review (BICR) |
2.66; 8.21; 2.96; 4.01; 2.79; 3.94 | — |
| SECONDARY Time to Progression (TTP) Rate Assessed by Blinded Independent Central Review (BICR) |
28.6; 60.0; 27.9; 33.9; 32.8; 41.5 | — |
| SECONDARY Progression Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) |
2.69; 8.97; 2.96; 4.01; 2.76; 3.94 | — |
| SECONDARY Overall Survival (OS) |
14.32; 36.27; 10.45; 26.68; 13.44; 17.45 | — |
| SECONDARY Overall Survival (OS) Rate |
69.6; 80.0; 53.3; 89.0; 75.4; 83.3 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) |
60.06; 19.81; 9.82; 100.74; 23.09; 15.54 | — |
| SECONDARY Time of Maximum Observed Serum Concentration (Tmax) |
3.00; 2.98; 3.00; 12.75; 12.28; 24.13 | — |
| SECONDARY Area Under the Serum Concentration Time Curve in the Dosing Interval [AUC(TAU)] |
9114.43; 2825.09; 1313.76; 15229.27; 3358.78; 3731.16 | — |
| SECONDARY Serum Concentration Achieved at the End of Dosing Interval (Trough Concentration) (Ctrough) |
16.52; 4.40; 2.26; 32.48; 6.76; 8.51 | — |
| SECONDARY Serum Concentration Achieved at the End of the Infusion (Ceoinf) |
49.88; 17.07; 6.99; 84.36; 25.53; 11.80 | — |
| SECONDARY Ratio of an Exposure Measure at Steady State to That After the First Dose (Exposure Measure Includes Cmax) (AI_Cmax) |
2.26; 1.53; 1.45 | — |
| SECONDARY Accumulation Index Ratio of AUC at Steady State to That After the First Dose (AI_AUC) |
2.60; 2.23; 2.28 | — |
| SECONDARY Effective T-Half (T-HALF) |
468.07; 382.36; 406.60 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies (ADA) |
0; 0; 0; 1; 0; 0 | — |
Summary
The first part of the study is the Dose Escalation Phase designed to establish the safety of nivolumab at different dose levels for each of the three cohorts (uninfected hepatocellular carcinoma (HCC) subjects, hepatitis C virus (HCV)-infected HCC subjects, and hepatitis B virus (HBV)-infected subjects).
The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses for each of the 3 cohorts. A third cohort has been added in this study to compare the efficacy of nivolumab and sorafenib in the treatment of Advanced HCC. A fourth cohort will generate data on the safety and efficacy of the combination nivolumab plus ipilimumab in the treatment of Advanced HCC. In the fifth cohort, additional clinical data will be generated for Child-Pugh B subjects. A Cabozantinib Combination Cohort has been added to evaluate the safety and tolerability of nivolumab in combination with cabozantinib and nivolumab with ipilimumab in combination with cabozantinib.
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria
- Subjects of 18 years or older (men and women) with histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
- Dose Escalation Phase: Child-Pugh score of 7 points or less. Cohort 5: Child-Pugh Class B (B7-B8). For all other cohorts Child-Pugh score of 6 points or less
Exclusion Criteria
- History of autoimmune disease
- Any prior or current clinically significant ascites
- Any history of hepatic encephalopathy
Data sourced from ClinicalTrials.gov (NCT01658878). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.