489TiP - BGB-LC-202 (NCT05577702): Phase II Umbrella study of tislelizumab (TIS) monotherapy and TIS-based immunotherapy combinations +/- chemotherapy (CT) as neoadjuvant treatment in Chinese patients (pts) with resectable stage II to IIIA non-small cell lung cancer (NSCLC)

Background

Neoadjuvant anti-programmed cell death (ligand) 1 (PD[L]-1) inhibitors + CT have shown promising efficacy improvements compared with CT alone in pts with resectable NSCLC. Exploring neoadjuvant treatment containing novel agents that retain or improve efficacy and minimize safety risks may provide more clinical options for these pts. This phase 2 study aims to evaluate the preliminary efficacy, safety, and pharmacodynamics of TIS, an anti-PD-1 monoclonal antibody (mAb), as monotherapy and in multiple immunotherapy combinations +/- CT as neoadjuvant treatment in pts with resectable NSCLC.

Trial design

This phase 2 randomized, open-label, multicenter study (14 sites) will enroll approximately 120 treatment-naïve pts aged ≥18 years with EGFR mutation and ALK-rearrangement-negative stage II to IIIA NSCLC. The umbrella design allows for multiple investigational drugs, administered alone or in combination in a single disease population. Pts will be allocated to 1 of 2 substudies based on tumor cell PD-L1 expression. Sixty pts in Substudy 1 (PD-L1 ≥50%) will be randomized 1:1:1 to TIS monotherapy (Arm 1A), TIS + ociperlimab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains mAb) (Arm 1B), or TIS + LBL-007 (anti-LAG-3 mAb) (Arm 1C). Sixty pts in Substudy 2 (PD-L1 <50%) will be randomized 1:2 to receive histology-specific (nonsquamous vs. squamous) CT in combination with TIS (Arm 2A) or TIS + LBL-007 (Arm 2C). All treatments will be administered on a 3-week cycle for 2–4 cycles followed by surgical resection and survival follow-up. The primary endpoint is major pathological response, per blinded independent pathology review (BIPR). Secondary endpoints include pathological complete response per BIPR, overall survival, event-free survival, and disease-free survival (both per investigator; RECIST v1.1), adverse events (per CTCAE v5.0), the proportion of pts who undergo surgical resection following treatment, and pharmacodynamic assessments of the investigational agents. Enrollment is ongoing.

Clinical trial identification

NCT05577702.

Legal entity responsible for the study

BeiGene.

Funding

BeiGene.

Disclosure

W. Yu: Financial Interests, Personal, Full or part-time Employment: BeiGene, BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene, BeiGene. J. Shi: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene. B. Wei: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene. W. Zheng: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene. Z. Shen: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene. All other authors have declared no conflicts of interest.