Clinical trial
A Phase 1/2, Dose-escalation, Open-label, Non-comparative Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Advanced Hepatocellular Carcinoma Subjects With or Without Chronic Viral Hepatitis; and a Randomized, Open-label Study of Nivolumab vs Sorafenib in Advanced Hepatocellular Carcinoma Subjects Who Are Naive to Systemic Therapy
Name
CA209-040
Description
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.
Trial arms
Trial start
2012-10-30
Estimated PCD
2024-06-28
Trial end
2024-06-28
Status
Active (not recruiting)
Phase
Early phase I
Treatment
Nivolumab
Arms:
Child-Pugh B, HBV-infected: Nivolumab, HCV-infected: Nivolumab, Nivolumab, Nivolumab plus Ipilimumab Combination, Non-infected: Nivolumab
Other names:
BMS-936558
Sorafenib
Arms:
Sorafenib
Ipilimumab
Arms:
Nivolumab plus Ipilimumab Combination
Cabozantinib
Arms:
Nivolumab plus Cabozantinib Combination, Nivolumab plus Ipilimumab plus Cabozantinib
Size
659
Primary endpoint
Safety of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
Tolerability of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
Objective response rate (ORR) for Expansion phase of nivolumab
Approximately 6 months minimum follow-up
ORR for Nivolumab vs Sorafenib Cohort
Approximately 6 months minimum follow-up
Safety of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
Tolerability of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
ORR for Nivolumab plus Ipilimumab Combination Cohort
Approximately 6 months minimum follow-up
ORR for Child-Pugh B Cohort
Approximately 6 months minimum follow-up
Safety of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
Tolerability of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities
100 days after last dose
ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort
Approximately 6 months minimum follow-up
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 659, 'type': 'ACTUAL'}}
Updated at
2023-12-14
1 organization
4 products
1 indication
Organization
Bristol-Myers SquibbProduct
NivolumabIndication
Hepatocellular CarcinomaProduct
SorafenibProduct
IpilimumabProduct
Cabozantinib