Linear Clinical Research | Perth, Australia
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This is an open-label, multicenter, nonrandomized Phase 1 and 2 clinical trial evaluating various combinations of BGB-A425 and/or LBL-007 with tislelizumab.
Full description
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.
TIM3, LAG3, 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 tumor infiltrating lymphocytes (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 (ie, 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 is strong scientific rationale that simultaneous targeting of these checkpoint blockers, could potentially increase therapeutic benefit and may help to overcome the resistance arising due to anti-PD-(L)-1 therapy. Hence, this study will evaluate the safety and preliminary efficacy of BGB-A425 (anti TIM-3), LBL-007 (Anti-LAG-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 safety lead-in will determine the RP2D for the combination of BGB-A425, Tislelizumab and/or LBL-007. Phase 2 dose expansion will continue to evaluate the safety but also focus on the efficacy of the doublet or triplet treatment combination in select tumor types.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria:
Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
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 • For NSCLC participants in Cohort 2, 5 and 7 (PD-L1 positive): Locally recurrent Stage IIIB, stage IIIC or Stage IV squamous or non-squamous non-small cell lung cancer
• For RCC participants in Cohort 3: Locally advanced unresectable or metastatic and histologically confirmed renal cell carcinoma with a clear cell histology
Key Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Primary purpose
Allocation
Interventional model
Masking
358 participants in 3 patient groups
Loading...
Central trial contact
BeiGene
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal