ABX196 in Combination With Nivolumab in Patients With Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Open-label, uncontrolled, phase 1-2 study to evaluate the safety, tolerability, pharmacodynamic effects, and preliminary efficacy of ABX196 administered in combination with nivolumab in patients with hepatocellular carcinoma

Detailed Description
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This is an open-label, uncontrolled phase 1-2 study to evaluate the safety, tolerability, pharmacodynamic effects, and preliminary efficacy of ABX196 administered in combination with nivolumab in patients with hepatocellular carcinoma. The study consists of 2 phases, a Dose Escalation Phase and an Expansion Phase. Nivolumab will be administered, consistent with the US prescribing information, as a 30-minute IV infusion on Days 1 and 15 of each 28-Day cycle. ABX196 will be administered as an IM injection 120 minutes (+/- 15 minutes) after the completion of the nivolumab infusion on Day 1 of every other 28-Day cycle (i.e., every 8 weeks).

Official Title
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A Phase 1-2 Study of ABX196 in Combination With Nivolumab in Patients With Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: ABX196


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women, Age ≥18 years Patients with ECOG performance status 0 or 1 Patients with histologically confirmed diagnosis of HCC not amenable to curative surgery or local therapy Patients with documented objective radiographic progression during or after local therapy or after treatment with sorafenib or lenvatinib or intolerance to or refusal to receive either agent Patients with at least one prior systemic therapy for HCC Patients eligible to be treated with nivolumab Patients with measurable disease based on RECIST v1.1 Patients with Child-Pugh class A liver score within 7 days of first study dose Patients with no history of hepatic encephalopathy Patients with no prior or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control (patients with ascites only on radiographic imaging are eligible) Patients with HBV infection must have received antiviral therapy for at least 12 weeks and HBV viral load must be documented to be <100 IU/mL within 7 days of first study dose Patients with no active co-infection with HBV and HCV or HBV and HDV Patients with no active drug or alcohol abuse Exclusion Criteria: Patients with tyrosine kinase inhibitor treatment within 2 weeks of first study dose Patients with esophageal or gastric variceal bleeding within the past 6 months Patients with portal vein invasion at the main portal (Vp4) or the inferior vena cava or cardiac involvement of HCC based on imaging Patients with previous solid organ or hematologic transplantation Patients with active autoimmune disease requiring systemic treatment in the past 2 years Patients with diagnosis of immunodeficiency or receiving systemic steroid therapy or other immunosuppressive therapy within 7 days before first study dose Patients with previous locoregional therapy or major surgery to the liver within 6 weeks before first study dose Patients with minor surgery to liver or another site within 1 week before first study dose

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX196<br>IM injection of 0.1, 0.2, and 0.4 µg of ABX196 | Drug: ABX196<br>* ABX196 will be administered as an IM injection 120 minutes (+/- 15 minutes) after the completion of the nivolumab infusion on Day 1 of every other 28-Day treatment cycle (i.e., every 8 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Adverse Events evaluated according to CTC-AE | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Partial and Complete response according to RECIST V1.1 | From date of randomization until the date of first documented progression, assessed up to 12 months | 
| Duration of Response (DOR) |  | From date of randomization until the date of first documented progression, assessed up to 12 months | 
| Progression-Free Survival |  | From date of randomization until the date of first documented progression, assessed up to 24 months | 
| Alpha Fetoprotein Serum concentrations |  | Every 2 weeks, assessed up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Nivolumab, ABX196