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: April 18, 2023
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: June 20, 2021
• First Posted Date: July 2, 2021
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: August 20, 2021
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 24, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 24, 2021)

• 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.
• 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.
• 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.
• 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)
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Investigating the Efficacy and Safety of Ociperlimab and Tislelizumab and BAT1706 Combinations in Patients With Advanced HCC
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Hepatocellular Carcinoma

Intervention

• 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

Study Arms

• 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
  Interventions:

  • Drug: Ociperlimab
  • Drug: Tislelizumab
  • Drug: BAT1706
• Experimental: Arm B: tislelizumab + BAT1706
  tislelizumab 200 mg intravenously once every 3 weeks followed by BAT1706 15 mg/kg intravenously once every 3 weeks
  Interventions:

  • Drug: Tislelizumab
  • Drug: BAT1706

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 24, 2021): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2023
• Estimated Primary Completion Date: August 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Taiwan

Administrative Information

• NCT Number: NCT04948697
• Other Study ID Numbers: AdvanTIG-206
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: BeiGene
• Verification Date: April 2023