Last updated on November 2019

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


Brief description of study

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 Study 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.

Clinical Study Identifier: NCT03744468

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