152P - Exploratory biomarker analysis of phase III ASTRUM-004 study: Serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer

Background

First-line serplulimab plus chemotherapy (chemo) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced squamous non-small-cell lung cancer (sqNSCLC) in the phase 3 ASTRUM-004 study. In this exploratory biomarker analysis, we retrospectively evaluated the association of genetic mutations with patient outcomes.

Methods

537 patients were randomized (2:1) in the trial. Genetic mutations were assessed by Med1CDx^TM panel in biomarker evaluable population (BEP) which included 309 patients (serplulimab-chemo, n = 212; placebo-chemo, n = 97). Median PFS and OS were estimated by Kaplan-Meier method in each biomarker subgroup. Comparisons between arms were performed, and HR and its 95% CI were estimated by a Cox proportional hazards model. Data cut-off date was Jan 31, 2023.

Results

Patient demographics in BEP were balanced between arms and were comparable to those in the intention-to-treat population. TP53 (85.4%), LRP1B (33.8%) and KMT2D (27.6%) were the most frequently mutated genes. Patients with mutations in Notch signalling pathway were associated with better confirmed objective response rate (74.1% vs 34.5%) and prolonged median PFS (16.7 vs 5.7 months, HR 0.42) in serplulimab-chemo arm compared with placebo-chemo arm, which was consistent with previous findings and possibly due to their roles in tumour microenvironment in sqNSCLC. Mutations in KMT2D, which is involved in modulating chromatin structure, as well as EPHA3 or PIK3C2G, which may regulate tumour microenvironment, were associated with better outcomes in serplulimab-chemo arm compared with placebo-chemo arm. In addition, better outcomes were observed in serplulimab-chemo arm regardless of KEAP1 mutation status, which on the contrary was found related to immune resistance in non-sqNSCLC.

Conclusions

The exploratory biomarker analysis suggests improved clinical benefit with the addition of serplulimab to chemo regardless of genetic mutation status. Furthermore, comparing to those without mutations, patients with mutations in Notch signalling pathway, KMT2D, PIK3C2G, or EPHA3 may derive more clinical benefit when serplulimab was added.

Clinical trial identification

NCT04033354.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

C. Zhou: Financial Interests, Personal, Advisory role, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc.; Financial Interests, Personal, Other, Payment or honoraria from: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics, AnHeart. L. Guo, F. Yang, Y. Liu, X. Yang, S. Zhong, Q. Wang, J. Li, Y. Shan, J. Zhu: Financial Interests, Personal and Institutional, Full or part-time Employment: Shanghai Henlius Biotech, Inc.. All other authors have declared no conflicts of interest.