A Randomized, Multi-center, Double-blinded, Placebo-controlled Phase 3 Study of Nivolumab and Ipilimumab, Nivolumab Monotherapy, or Placebo in Combination With Trans-arterial ChemoEmbolization (TACE) in Patients With Intermediate-stage Hepatocellular Carcinoma (HCC)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 26
- Locations
- 89
- Primary Endpoint
- Number of Participants With Adverse Events
Study Overview
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of nivolumab with and without ipilimumab in combination with Trans-arterial ChemoEmbolization (TACE) to TACE alone in participants with intermediate liver cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant has intermediate-stage hepatocellular carcinoma (HCC) whose tumor characteristics exceed the Beyond Milan and Up-to-7 (BMU7) criteria and is eligible for trans-arterial ChemoEmbolization (TACE)
- •Participant has no extrahepatic spreading (EHS), no regional lymph node involvement, no main, left main, or right main portal vein thrombosis, and no macrovascular invasion (MVI)
- •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 or participants who are on the waiting list for liver transplantation
- •Active, known, or suspected autoimmune disease
- •Other protocol defined inclusion/exclusion criteria apply
Arms & Interventions
Nivolumab + Ipilimumab + TACE
TACE (Trans-arterial ChemoEmbolization)
Intervention: nivolumab (Drug)
Nivolumab + Ipilimumab + TACE
TACE (Trans-arterial ChemoEmbolization)
Intervention: ipilimumab (Drug)
Nivolumab + Ipilimumab + TACE
TACE (Trans-arterial ChemoEmbolization)
Intervention: TACE (Procedure)
Nivolumab + TACE
Intervention: nivolumab (Drug)
Nivolumab + TACE
Intervention: TACE (Procedure)
TACE
Intervention: TACE (Procedure)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Number of Participants With Serious Adverse Events (SAEs)
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose that results in death, Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) or requires inpatient hospitalization or causes prolongation of existing hospitalization, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event.
Number of Participants Who Died
Time Frame: From first dose and 100 days after last dose of study therapy (up to approximately 27 months)
Number of participants who died due to any cause are summarized.
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Number of Participants With Worst Grade (Grade 3/4) Laboratory Results
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 =Severe, Grade 4 = Life-threatening). Highest grade measured for hemoglobin and albumin was Grade 3.
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Blood samples were collected for specific thyroid test.
Number of Participants With Clinical Laboratory Abnormalities in Specific Liver Tests
Time Frame: From first dose and 30 days after last dose of study therapy (up to approximately 25 months)
Blood samples were collected for specific liver tests.
Secondary Outcomes
No secondary outcomes reported