Clinical Trials /

Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors

NCT03744468

Description:

BGB-A425 is a humanized, IgG1-variant monoclonal antibody against TIM-3. Tislelizumab is a humanized, IgG4-variant monoclonal antibody against PD-1. This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors
  • Official Title: Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-TIM-3 Monoclonal Antibody BGB-A425 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BGB-900-102
  • NCT ID: NCT03744468

Conditions

  • Locally Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
BGB-A425Phase 1 Dose Escalation
tislelizumabBGB-A317Phase 1 Dose Escalation

Purpose

BGB-A425 is a humanized, IgG1-variant monoclonal antibody against TIM-3. Tislelizumab is a humanized, IgG4-variant monoclonal antibody against PD-1. This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors.

Detailed Description

      Blocking antibodies targeting PD-1 have achieved remarkable results in the treatment of many
      types of tumors. However, it is also worth noting that this therapeutic strategy typically
      achieves a < 30% objective response rate (ORR) as a monotherapy in patients whose tumors
      exhibit low positive PD-L1 expression and/or are microsatellite stable. TIM-3 and PD-1
      function as immune checkpoint receptors in the overlapping regulation of immune tolerance and
      have been shown to be overexpressed on the tumor infiltrating lymphocytes (TILs) from patient
      samples of various solid tumors including, but not limited to non-small cell lung cancer,
      head and neck squamous cell carcinoma, hepatocellular carcinoma, and gastric carcinoma.
      Subsequently, the activation of TIM-3 and PD-1 represent TILs from both patients or animals
      across solid tumor types with the most exhausted immunophenotype (ie, cytokine expression,
      proliferation etc.), which can be reversed with combined blockade of TIM-3 and PD 1. The
      overlap in expression and function indicates that TIM-3 and PD-1 cooperate to promote
      effector cell exhaustion which may impede an effective antitumor immune response. Based upon
      the overlapping expression profiles and immuno-regulatory functions, the improved in vivo
      antitumor effects, as well as the potential for TIM-3 mediated adaptive resistance, there is
      strong scientific rationale to evaluate the antitumor effects derived from the combined
      blockade of TIM-3 and PD-1 in advanced solid tumors. Accordingly, this study will evaluate
      the safety and preliminary efficacy of BGB-A425 (anti TIM-3) in combination with tislelizumab
      (anti PD-1) in patients with advanced solid tumors.

      This is an open-label, multicenter, nonrandomized Phase 1 and Phase 2 clinical trial. Phase 1
      will determine the Recommended Phase 2 Dose (RP2D) for the combination of BGB-A425 and
      tislelizumab. Phase 2 will continue to evaluate the safety but also focus on the efficacy of
      the combination in select tumor types.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose EscalationExperimentalDose escalation of BGB-A425 in combination with tislelizumab in patients with advanced solid tumors
  • BGB-A425
  • tislelizumab
Phase 2 Dose ExpansionExperimentalFurther explore the safety and clinical activity of BGB-A425 in combination with tislelizumab in patients with select advanced solid tumors
  • BGB-A425
  • tislelizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histologically or cytologically confirmed advanced, metastatic,
             unresectable solid tumors who have previously received standard systemic therapy or
             for which treatment is not available, not tolerated or refused.

          2. Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.

          3. Has adequate organ function.

        Exclusion Criteria:

          1. Active brain or leptomeningeal metastasis.

          2. Active autoimmune diseases or history of autoimmune diseases that may relapse.

          3. With severe chronic or active infections requiring systemic antibacterial, antifungal
             or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is
             permitted for patients with hepatocellular carcinoma).

          4. Concurrent participation in another therapeutic clinical trial.

          5. Received prior therapies targeting TIM-3.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 Dose Escalation
Time Frame:Approximately 1.5 years
Safety Issue:
Description:Safety and tolerability of BGB-A425 in combination with tislelizumab using Common Terminology Criteria for Adverse Events (CTCAE v.5.0) in patients with advanced solid tumors.

Secondary Outcome Measures

Measure:Duration of response (DOR)
Time Frame:Phase 1 or 2 Expansion - Approximately 1.5 years each
Safety Issue:
Description:Duration of response (DOR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.
Measure:Disease control rate (DCR)
Time Frame:Phase 1 or 2 Expansion - Approximately 1.5 years each
Safety Issue:
Description:Disease control rate (DCR) will be determined from investigator derived tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1.
Measure:Progression free survival
Time Frame:Phase 2 Expansion - Approximately 3 years
Safety Issue:
Description:Progression free survival will be determined from investigator derived tumor assessments per RECIST 1.1.
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: AUC, 0 to 21 days
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: Minimum Concentration (Cmin)
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: Maximum Concentration (Cmax)
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: Clearance (CL)
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2-Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: Volume of Distribution (Vz)
Measure:PK Parameter
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:PK Parameter: terminal half-life (t1/2)
Measure:Immunogenicity
Time Frame:Phase 1 and Phase 2- Approximately 1.5 year each
Safety Issue:
Description:Immunogenicity as assessed by the presence of anti-drug antibodies

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

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