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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Ociperlimab; Drug: Tislelizumab; Drug: BAT1706

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong, China
    • Nanfang Hospital of Southern Medical University
  • Jiangxi, China
    • The Second Affiliated Hospital of Nanchang University
  • Zhejiang, China
    • Hwa Mei Hospital, University of Chinese Academy of Sciences
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing University Three Gorges Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Fuzhou
    • Gulou, Fuzhou, China
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110022
      • Shengjing Hospital of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Zhongshan Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300070
      • Tianjin Medical University Cancer Institute & Hospital
    • Tianjin, Tianjin, China
      • Tianjin Third Central Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The second affiliated hospital of zhejiang university school of medicine
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan, Taiwan, 710
    • Chi Mei Medical Center
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Medical Foundation (CGMF) - Linkou Branch

Participation Criteria

Eligibility Criteria

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

Description

Criteria:

Inclusion Criteria:

1. Histologically confirmed HCC
2. 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. Tumor tissue required for an evaluable PD-L1 expression result
4. No prior systemic therapy for HCC
5. At least 1 measurable lesion as defined per RECIST v1.1
6. Adequate organ function during screening and before randomization

Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
2. Prior therapy with antibody or drug specifically targeting T-cell costimulation or checkpoint pathway; prior treatment with bevacizumab or its biosimilars
3. Prior history of ≥ Grade 2 hepatic encephalopathy
4. Leptomeningeal disease or uncontrolled, untreated brain metastasis
5. Active autoimmune diseases or history of autoimmune diseases that may relapse
6. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases
7. Infection (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days of randomization
8. Prior allogeneic stem cell transplantation or organ transplantation
9. Significant cardiovascular risk factors
10. Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk of bleeding
11. History of severe hypersensitivity reactions to other monoclonal antibodies
12. Administered a live vaccine ≤ 28 days before randomization

NOTE: Other protocol Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Vincent Li, MD, BeiGene, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: June 20, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: AdvanTIG-206; CTR20211546 (Registry Identifier: ChinaDrugTrials)

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