Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The primary objective of this study is to assess the preliminary antitumor activity as indicated by overall response rate (ORR) of tislelizumab in combination with lenvatinib in participants with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC).

Official Title
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A Phase 2 Study to Investigate the Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib in Patients With Unresectable Locally Advanced or Metastatic Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, Unresectable Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Lenvatinib
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Unresectable locally advanced or metastatic HCC, which must be confirmed by histologically or cytologically. Fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma histology confirmed by histologically or cytologically is excluded. Barcelona Clinic Liver Cancer (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 Did not receive any systemic treatment before and is unwilling to accept standard of care treatment or not suitable for standard of care treatment as judged by investigators European Cancer Oncology Group (ECOG) Performance Status ≤ 1 Child-Pugh A classification for liver function assessed within 7 days of first dose of study drugs Key Exclusion Criteria: Active autoimmune diseases or history of autoimmune diseases that may relapse Any active malignancy ≤ 2 years before the first dose of study drugs except for specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast) Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management, or ≥ Grade 3 hypoalbuminemia ≤ 14 days before the first dose of study drugs Any known brain or leptomeningeal metastases Concurrent participation in another therapeutic clinical study NOT: Other protocol defined Inclusion/Exclusion criteria may apply NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Safety Run-in<br>Lenvatinib at a dose of 8 mg or 12 mg based on body weight + tislelizumab for one 21-day cycle | Drug: Lenvatinib<br>* Capsules administered orally once daily<br>Drug: Tislelizumab<br>* 200 mg intravenous (IV) infusion administered on Day 1 of each cycle<br>|
| Experimental: Part 2: Lenvatinib<br>Lenvatinib at the recommended phase 2 dose (RP2D) determined from Part 1 + tislelizumab in 21-day cycles for up to 12 months | Drug: Lenvatinib<br>* Capsules administered orally once daily<br>Drug: Tislelizumab<br>* 200 mg intravenous (IV) infusion administered on Day 1 of each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) as assessed by Central Imaging Facility based on RECIST v1.1 |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing Adverse Events (AEs) |  | Up to 12 months | 
| Number of participants experiencing Severe Adverse Events (SAEs) |  | Up to 12 months | 
| Overall Response Rate (ORR) |  | Up to 12 months | 
| Duration Of Response (DOR) |  | Up to 12 months | 
| Disease Control Rate (DCR) |  | Up to 12 months | 
| Progression-Free Survival (PFS) |  | Up to 12 months |