NCT03744468

Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors

Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Various Combinations of BGB-A425 and LBL-007 With Tislelizumab in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 147 (actual)
• Sponsor: BeiGene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of surzebiclimab (BGB-A425) and/or alcestobart (LBL-007) with tislelizumab.

Detailed description

Blocking antibodies targeting programmed cell death protein-1 (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 was apparent that additional immuno-regulatory mechanism(s) underlie tumor immune escape. Indeed, research shows that the T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) pathway cooperates with PD-1 to maximize the suppression of effector tumor infiltrating lymphocytes (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 participants. TIM-3, Lymphocyte activation gene-3 (LAG-3), and PD-1 function as immune checkpoint receptors in the overlapping regulation of immune tolerance and have been shown to be co-overexpressed on the TILs from the participant samples of various solid tumors. Furthermore, emerging clinical data and preclinical data demonstrate co-expression of TIM-3, LAG-3, PD-1 often yield T cells exhausted immunophenotype (i.e., cytokine expression, proliferation etc.). Cancer cells take advantage of PD-1, TIM-3, and LAG-3 in inhibiting immune cells' function, and escape the immune surveillance. Based upon the overlapping expression profiles and immuno-regulatory functions, TIM-3 and LAG-3 mediated adaptive resistance, there was strong scientific rationale that simultaneous targeting of these checkpoint blockers, could potentially increase therapeutic benefit and might help to overcome the resistance arising due to anti-PD-(L)-1 therapy. Hence, this study evaluated the safety and preliminary efficacy of surzebiclimab (anti TIM-3), alcestobart (Anti-LAG-3) in combination with tislelizumab (anti PD-1) in patients with advanced solid tumors. This was an open-label, multicenter, nonrandomized Phase 1 and Phase 2 clinical trial. Phase 1 determined the recommended phase 2 dose (RP2D) for the combination of surzebiclimab and tislelizumab. Phase 2 safety lead-in determined the RP2D for the combination of surzebiclimab, tislelizumab and/or alcestobart. Phase 2 dose expansion continued to evaluate the safety but also focus on the efficacy of the doublet or triplet treatment combination in select tumor types.

Conditions

• Locally Advanced or Metastatic Solid Tumors for Phase 1, Dose Escalation and Phase 2 Safety Lead-in
• HNSCC for Phase 2 Dose Expansion
• NSCLC for Phase 2 Dose Expansion

Interventions

Type	Name	Description
DRUG	Surzebiclimab	Humanized immunoglobulin G1 (IgG1)-variant monoclonal antibody against TIM-3
DRUG	Tislelizumab	Humanized, IgG4-variant monoclonal antibody against PD-1
DRUG	Alcestobart	Human anti LAG-3 antibody

Timeline

• Start date: 2018-11-13
• Primary completion: 2025-02-06
• Completion: 2025-02-06
• First posted: 2018-11-16
• Last updated: 2026-04-02
• Results posted: 2026-04-02

Locations

40 sites across 6 countries: United States, Australia, France, Italy, South Korea, Spain

Regulatory

• FDA-regulated drug study