A phase II trial of tobemstomig (tobe) plus platinum-based chemotherapy (chemo) vs pembrolizumab (pembro) plus chemo in patients (pts) with untreated locally advanced or metastatic non-small cell lung cancer (NSCLC)

Document Type

Conference Proceeding

Publication Date

3-1-2025

Abstract

Background: Tobemstomig (tobe) is a novel bispecific antibody targeting programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3). BO44178 (NCT05775289) is a randomised, double-blind, phase II study evaluating tobe + chemo vs pembro + chemo in pts with NSCLC who are ineligible for surgery or definitive chemoradiotherapy. Methods: Eligible pts with previously untreated, locally advanced unresectable or metastatic NSCLC were randomised 1:1 to receive either induction tobe + chemo (carboplatin + paclitaxel/pemetrexed) or pembro + chemo for four 21-day cycles, followed by maintenance tobe or pembro with/without pemetrexed every 3 weeks until disease progression, toxicity or loss of clinical benefit. Pts were stratified by PD ligand 1 expression, histology and smoking status. Primary endpoints: confirmed objective response rate (ORR); progression-free survival (PFS). Secondary endpoints included overall survival (OS), duration of response (DoR) and safety. Results: At data cutoff (20 June 2024), 181 pts were randomised to receive tobe + chemo (n = 90) or pembro + chemo (n = 91). Median duration of follow-up was 6 months. Baseline characteristics were similar across treatment arms; median age was 66 years. There was no improvement in confirmed ORR with tobe + chemo (41.1%) vs pembro + chemo (46.2%) and no PFS difference was observed between treatment arms (HR 0.99; 95% CI 0.63, 1.56; Table). OS data were immature at this analysis. Efficacy results were consistent across subgroups. The rates of grade 3/4 adverse events (AEs), serious AEs and immune-mediated AEs were higher with tobe + chemo vs pembro + chemo; however, the rate of treatment withdrawal due to AEs was similar between arms. Conclusions: At this interim analysis, no ORR or PFS benefit was observed in pts with untreated locally advanced or metastatic NSCLC receiving tobe + chemo over pembro + chemo. OS data remain immature.

Issue

3 suppl 1

First Page

S11

Last Page

S12

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