Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors
BGB-A425 is a humanized, immunoglobulin gamma-1 (IgG1)-variant monoclonal antibody against TIM-3. Tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against PD-1. This study tests the safety and anti-tumor effect of BGB-A425 in combination with tislelizumab in participants with advanced solid tumors.
- Locally Advanced or Metastatic Solid Tumors for Phase 1 HNSCC, NSCLC and RCC for Phase 2
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Phase 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. Phase 2: Patients with one of the following histologically or cytologically confirmed solid tumors: Cohort 1 (HNSCC, PD-L1 positive): Recurrent/metastatic head and neck squamous cell cancer of the oral cavity, oropharynx, hypopharynx, and/or larynx whose tumor is not amenable to local therapy with curative intent (ie, surgery or radiation therapy with or without chemotherapy Cohort 2 (NSCLC, PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer Cohort 3 (RCC): Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis. - Active autoimmune diseases or history of autoimmune diseases that may relapse. - With infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug(s), or a requirement for chronic prophylactic treatment with antibiotics. - Concurrent participation in another therapeutic clinical trial. 6. Received prior therapies targeting TIM-3. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 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.
- Primary Purpose
- None (Open Label)
- Masking Description
- Open Label
Phase 1 Dose Escalation
|Dose escalation of BGB-A425 in combination with tislelizumab in participants with advanced solid tumors||
Phase 2 Dose Expansion
|Further explore the safety and clinical activity of BGB-A425 in combination with tislelizumab in participants with NSCLC, HNSCC and RCC.||
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Blocking antibodies targeting PD-1 have achieved remarkable results in the treatment of many types of tumors. However, based upon the rate of primary and secondary resistance to PD-1 blockade, it is apparent that additional immuno-regulatory mechanism(s) underlie tumor immune escape. Indeed, research shows that the TIM-3 pathway cooperates with PD-1 to maximize the suppression of effector TILs as well as promote resistance to anti-PD-1 therapy. Therefore, TIM-3 represents an ideal target with the potential to significantly improve and/or extend the therapeutic benefit of anti-PD-1 therapy to a greater number of patients. 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 participant samples of various solid tumors including, but not limited to non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, hepatocellular carcinoma, and gastric carcinoma. Subsequently, the activation of TIM-3 and PD-1 represent TILs from both participants 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 participants 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.