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

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Lenvatinib; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510060
    • Sun Yat-sen University - Cancer Center (SYSUCC)
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi 'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital ,Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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.
2. 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
3. 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
4. European Cancer Oncology Group (ECOG) Performance Status ≤ 1
5. Child-Pugh A classification for liver function assessed within 7 days of first dose of study drugs

Key Exclusion Criteria:

1. Active autoimmune diseases or history of autoimmune diseases that may relapse
2. 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)
3. 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
4. Any known brain or leptomeningeal metastases
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): February 18, 2024

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Lenvatinib; Tislelizumab
• Other Study ID Numbers: BGB-A317-211; CTR20200972 (Registry Identifier: ChiCTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No