Study of Surzebiclimab (BGB-A425) and Alcestobart (LBL-007) in Combination With Tislelizumab in Advanced Solid Tumors
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.
Inclusion Criteria
- Participants were aged >=18 years.
- Adequate organ function.
- Eastern Cooperative Oncology Group (ECOG) performance status <=1.
- Must have been able to provide a recently obtained archival tumor tissue or fresh tumor biopsy.
- The phase 1 dose escalation and phase 2 safety lead-in enrolled participants with histologically/cytologically confirmed advanced/metastatic solid tumors who had previously received standard systemic therapy per local guidelines, unless it was not available, not tolerated or determined not appropriate based on investigators judgement, and had at least 1 evaluable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- The phase 2 dose expansion enrolled participants with recurrent/metastatic HNSCC (Cohorts 1 and 4) and advanced/metastatic NSCLC (Cohorts 2 and 5), with disease progression that occurred >=10 weeks from the initiation of anti-PD-1/PD-L1 treatment for locally advanced or metastatic disease and had at least 1 measurable lesion outside of the central nervous system per RECIST v1.1. Key
Exclusion Criteria
- A history of severe hypersensitivity reactions to other monoclonal antibodies.
- Active autoimmune disease or a history of autoimmune diseases that might relapse or a history of life-threatening toxicity related to prior immune therapy.
- Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication <=14 days before administration of study drug.
- A history of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases.
- Prior therapy targeting TIM-3 and/or LAG-3.
- The phase 2 dose expansion NSCLC cohorts excluded participants with known sensitizing epidermal growth factor receptor (EGFR) mutation, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, anaplastic lymphoma kinase (ALK) fusion, or c-ros oncogene 1 (ROS1) fusion. NOTE: Other protocol defined Inclusion/Exclusion criteria might apply.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03744468.
Locations matching your search criteria
United States
North Carolina
Chapel Hill
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.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationBeiGene
- Primary IDBGB-900-102
- Secondary IDsNCI-2019-00104, 2018-001922-24, 2022-500694-14, U1111-1278-0027
- ClinicalTrials.gov IDNCT03744468