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

• ClinicalTrials.gov Identifier: NCT04948697
• Recruitment Status: Active, not recruiting
• First Posted: July 2, 2021
• Last Update Posted: July 15, 2022
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Hepatocellular Carcinoma	Drug: Ociperlimab; Drug: Tislelizumab; Drug: BAT1706	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 20, 2021
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: August 2023

Arms and Interventions

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 Name: BGB-A1217; Drug: Tislelizumab; 200 mg intravenously once every 3 weeks (dosed in 21-day cycles); Other Name: BGB-A317; Drug: BAT1706; 15 mg/kg intravenously once every 3 weeks (dosed in 21-day cycles); Other Name: 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 Name: BGB-A317; Drug: BAT1706; 15 mg/kg intravenously once every 3 weeks (dosed in 21-day cycles); Other Name: Bevacizumab Injection

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) as assessed by the investigator [ Time Frame: 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 ]
   defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST v1.1

Secondary Outcome Measures :

1. Duration of Response (DOR) as assessed by the investigator [ Time Frame: time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first. assessed up to 24 months ]
   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.
2. TIme to Response (TTR) as assessed by the investigator [ Time Frame: time from the date of first dose of study drug to the first documentation of response, assessed up to 24 months ]
   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.
3. Disease Control Rate (DCR) as assessed by the investigator [ Time Frame: time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first, assessed up to 24 months ]
   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.
4. Clinical Benefit Rate (CBR) [ Time Frame: time from the first confirmed objective response until the first documentation of disease progression or death, whichever comes first, assessed up to 24 months ]
   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)
5. PFS as assessed by the investigator [ Time Frame: 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 ]
   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
6. Overall Survival (OS) [ Time Frame: time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months ]
   measured time from the date of the first dose of study drug until the date of death from any cause
7. Incidence and severity of adverse events (AEs), [ Time Frame: time from the date of the first dose of study drug until the date of death from any cause, assessed up to 24 months ]
   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
8. Serum concentrations of ociperlimab at specified timepoints [ Time Frame: Through study completion, up to 24 months ]
   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
9. Serum concentrations of tislelizumab at specified timepoints [ Time Frame: Through study completion, up to 24 months ]
   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
10. Serum concentrations of BAT1706 at specified timepoints [ Time Frame: Through study completion, up to 24 months ]
    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
11. Immunogenic Response to ociperlimab [ Time Frame: Through study completion, up to 24 months ]
    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
12. Immunogenic Response to tislelizumab [ Time Frame: Through study completion, up to 24 months ]
    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
13. Immunogenic Response to BAT1706 [ Time Frame: Through study completion, up to 24 months ]
    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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

China, Beijing

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing, China, 100021

Beijing Cancer Hospital

Beijing, Beijing, China, 100142

China, Chongqing

Chongqing University Three Gorges Hospital

Chongqing, Chongqing, China

China, Fujian

Fujian Cancer Hospital

Fuzhou, Fujian, China, 350014

China, Fuzhou

Mengchao Hepatobiliary Hospital of Fujian Medical University

Gulou, Fuzhou, China

China, Guangdong

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China, 510080

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

China, Heilongjiang

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China, 150000

China, Hubei

Hubei Cancer Hospital

Wuhan, Hubei, China

China, Hunan

Hunan Cancer Hospital

Changsha, Hunan, China, 410006

China, Liaoning

The First Hospital of China Medical University

Shenyang, Liaoning, China, 110001

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China, 110022

China, Shanghai

Fudan University Zhongshan Hospital

Shanghai, Shanghai, China, 200032

China, Sichuan

West China Hospital Sichuan University

Chengdu, Sichuan, China, 610041

China, Tianjin

Tianjin Medical University Cancer institute & Hospital

Tianjin, Tianjin, China, 300070

Tianjin Third Central Hospital

Tianjin, Tianjin, China

China, Zhejiang

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China, 310009

China

Nanfang Hospital of Southern Medical University

Guangdong, China

The Second Affiliated Hospital of Nanchang University

Jiangxi, China

Hwa Mei Hospital, University of Chinese Academy of Sciences

Zhejiang, China

Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan, 704

Chi Mei Medical Center

Tainan, Taiwan, 710

National Taiwan University Hospital

Taipei, Taiwan, 100

Taipei Veterans General Hospital

Taipei, Taiwan, 112

Chang Gung Medical Foundation (CGMF) - Linkou Branch

Taoyuan, Taiwan, 33305

Sponsors and Collaborators

BeiGene

Investigators

• Study Director: Vincent Li, MD; BeiGene, Ltd.

More Information

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT04948697
• Other Study ID Numbers: AdvanTIG-206
• First Posted: July 2, 2021
• Last Update Posted: July 15, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors