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

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.

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.