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 (CheckMate040)

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Sorafenib; Biological: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01658878

2012-001514-42 (EudraCT Number)

CA209-040

Details and patient eligibility

About

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.

Full description

Study Classification: Pharmacokinetics/Pharmacodynamics

Enrollment: 659 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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659 participants in 9 patient groups

Non-infected: Nivolumab

Experimental group

Description:

Nivolumab intravenous solution on specific days

Treatment:

Biological: Nivolumab

HCV-infected: Nivolumab

Experimental group

Description:

Nivolumab intravenous solution on specific days

Treatment:

Biological: Nivolumab

HBV-infected: Nivolumab

Experimental group

Description:

Nivolumab intravenous solution on specific days

Treatment:

Biological: Nivolumab

Nivolumab

Experimental group

Description:

Nivolumab intravenous solution on specific days

Treatment:

Biological: Nivolumab

Sorafenib

Active Comparator group

Description:

Sorafenib tablets on specific days

Treatment:

Drug: Sorafenib

Nivolumab plus Ipilimumab Combination

Experimental group

Description:

Nivolumab intravenous solution + Ipilimumab intravenous solution on specific days

Treatment:

Drug: Ipilimumab

Biological: Nivolumab

Child-Pugh B

Experimental group

Description:

Nivolumab intravenous solution on specific days

Treatment:

Biological: Nivolumab

Nivolumab plus Cabozantinib Combination

Experimental group

Description:

Nivolumab intravenous solution + cabozantinib oral tablets on specific days

Treatment:

Drug: Cabozantinib

Nivolumab plus Ipilimumab plus Cabozantinib

Experimental group

Description:

Nivolumab intravenous solution + Ipilimumab intravenous solution + cabozantinib oral tablets on specific days

Treatment:

Drug: Cabozantinib