A Study Investigating the Efficacy and Safety of Ociperlimab and Tislelizumab and BAT1706 Combinations in Patients With Advanced HCC

Study Overview
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Brief Summary
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This is a Phase 2, randomized, multicenter, open-label, 2-arm study to investigate the efficacy and safety of ociperlimab in combination with tislelizumab plus BAT1706, and tislelizumab plus BAT1706, as first-line treatment in participants with advanced HCC.

Official Title
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A Phase 2, Randomized, Open-labeled Clinical Study Investigating the Efficacy and Safety of Ociperlimab in Combination With Tislelizumab Plus BAT1706 and of Tislelizumab Plus BAT1706 as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Ociperlimab
* Drug: Tislelizumab
* Drug: BAT1706


Participation Criteria
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Eligibility Criteria
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Criteria: Inclusion Criteria: Histologically confirmed HCC BCLC Stage C disease, or BCLC Stage B disease that is not amenable to or has progressed after loco-regional therapy, and is not amenable to a curative treatment approach Tumor tissue required for an evaluable PD-L1 expression result No prior systemic therapy for HCC At least 1 measurable lesion as defined per RECIST v1.1 Adequate organ function during screening and before randomization Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology Prior therapy with antibody or drug specifically targeting T-cell costimulation or checkpoint pathway; prior treatment with bevacizumab or its biosimilars Prior history of ≥ Grade 2 hepatic encephalopathy Leptomeningeal disease or uncontrolled, untreated brain metastasis Active autoimmune diseases or history of autoimmune diseases that may relapse History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases Infection (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days of randomization Prior allogeneic stem cell transplantation or organ transplantation Significant cardiovascular risk factors Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding History of severe hypersensitivity reactions to other monoclonal antibodies Administered a live vaccine ≤ 28 days before randomization NOTE: Other protocol Inclusion/Exclusion criteria may apply

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: ociperlimab + tislelizumab + BAT1706<br>tislelizumab 200 mg intravenously once every 3 weeks followed by BAT1706 15 mg/kg intravenously once every 3 weeks followed by ociperlimab 900 mg intravenously once every 3 weeks | Drug: Ociperlimab<br>* 900 mg intravenously once every 3 weeks (dosed in 21-day cycles)<br>* Other names: BGB-A1217;Drug: Tislelizumab<br>* 200 mg intravenously once every 3 weeks (dosed in 21-day cycles)<br>* Other names: BGB-A317;Drug: BAT1706<br>* 15 mg/kg intravenously once every 3 weeks (dosed in 21-day cycles)<br>* Other names: Bevacizumab Injection;|
| Experimental: Arm B: tislelizumab + BAT1706<br>tislelizumab 200 mg intravenously once every 3 weeks followed by BAT1706 15 mg/kg intravenously once every 3 weeks | Drug: Tislelizumab<br>* 200 mg intravenously once every 3 weeks (dosed in 21-day cycles)<br>* Other names: BGB-A317;Drug: BAT1706<br>* 15 mg/kg intravenously once every 3 weeks (dosed in 21-day cycles)<br>* Other names: Bevacizumab Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) as assessed by the investigator | defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 | Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) as assessed by the investigator | DOR is the time from the date of first documentation of a partial response (PR) or better to the date of first documentation of progressive disease (PR or better). DOR will be assessed based on RECIST v1.1. | time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first. assessed up to 24 months | 
| TIme to Response (TTR) as assessed by the investigator | TTR is defined as the time from the date of first dose administration to the date of first documented partial response (PR) or better by the investigator. TTR will be assessed based on RECIST v1.1. | time from the date of first dose of study drug to the first documentation of response, assessed up to 24 months | 
| Disease Control Rate (DCR) as assessed by the investigator | DCR is defined as the percentage of participants who achieve complete response (CR), partial response (PR) or durable stable disease (stable disease defined as greater than or equal to (≥) 24 weeks)). The DCR will be assessed based on RECIST v1.1. | time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first, assessed up to 24 months | 
| Clinical Benefit Rate (CBR) | defined as the proportion of participants who achieve complete response (CR), partial response (PR), or durable stable disease (stable disease defined as greater than or equal to (≥) 24 weeks) | time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first, assessed up to 24 months | 
| PFS as assessed by the investigator | PFS will be evaluated by the investigator according to RECIST version 1.1. PFS is defined as the time from the date of first dose to the date of first documentation of disease progression or date of death from any cause, whichever occurs first | time from the date of the first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first, assessed up to 24 months | 
| Overall Survival (OS) | measured time from the date of the first dose of study drug until the date of death from any cause | time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months | 
| Incidence and severity of adverse events (AEs), | severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version [v] 5.0, vital signs and clinical laboratory test results | time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months | 
| Serum concentrations of ociperlimab at specified timepoints | Collected at time intervals: predose on Day 1 of Cycles 1, 2, 5, 9 and 17. Postdose on Day 1 of Cycles 1 and 5 and Safety Follow-up Visit | Through study completion, up to 24 months | 
| Serum concentrations of tislelizumab at specified timepoints | Collected at time intervals: predose on Day 1 of Cycles 1, 2, 5, 9 and 17. Postdose on Day 1 of Cycles 1 and 5 and Safety Follow-up Visit | Through study completion, up to 24 months | 
| Serum concentrations of BAT1706 at specified timepoints | Collected at time intervals: predose on Day 1 of Cycles 1,2, 5, 9, and 17. Postdose on Day 1of Cycles 1 and 5 and EOT Visit | Through study completion, up to 24 months | 
| Immunogenic Response to ociperlimab | evaluated through detection of antidrug antibodies (ADAs). Time to onset of immunogenic response will be reported Collected at time intervals: predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at Safety Follow-up Visit | Through study completion, up to 24 months | 
| Immunogenic Response to tislelizumab | evaluated through detection of antidrug antibodies (ADAs). Time to onset of immunogenic response will be reported Collected at time intervals: predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at Safety Follow-up Visit | Through study completion, up to 24 months | 
| Immunogenic Response to BAT1706 | evaluated through detection of antidrug antibodies (ADAs). Time to onset of immunogenic response will be reported Collected at time intervals: predose on Day 1 of Cycles 1, 2, 5, 9 and 17, and at EOT Visit | Through study completion, up to 24 months |