Sosimerasib monotherapy in patients with previously treated KRAS G12C–mutated non-small cell lung cancer: Primary results of a phase 2 study.

Abstract

8520 Background: KRAS G12C mutation is a poor prognostic factor for Non-Small Cell Lung Cancer (NSCLC). Sosimerasib is a novel potent and highly selective KRAS G12C inhibitor. Here we report the primary results from a Phase 2 study of sosimerasib in patients with advanced NSCLC harboring the KRAS G12C mutation. Methods: In this open-label, multicenter, single-arm, pivotal phase 2 study, patients with locally advanced/metastatic KRAS G12C mutated NSCLC after failure with platinum-based chemotherapy and/or anti-PD-1/PD-L1 inhibitors were enrolled and treated with sosimerasib 500mg orally once daily. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST v1.1. The secondary endpoints included duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 145 patients were enrolled. The median age was 63 years, 85.5% were male, and previous treatment lines ranged from 1 to 3, with 84.1% patients having received both platinum-based chemotherapy and anti-PD-1/PD-L1 inhibitors. By 3 November 2024, the median follow-up duration was 6.8 months (range: 0.4-10.9). IRC-confirmed ORR was 52.4% (95% CI: 44.0-60.8) with median TTR of 1.4 months (range: 1.2-8.4), DCR was 87.6% (95% CI: 81.1-92.5). Median PFS was 7.2 months (95% CI: 5.6-NA). Median DOR and median OS were not reached. At the data cutoff date, Treatment-related adverse events (TRAEs) were reported in 138 (95.2%) patients, grade 3-4 TRAEs occurred in 58 (40.0%) patients. No TRAE was fatal. Most common TRAEs were alanine aminotransferase increased (66.2%), aspartate aminotransferase increased (62.8%), anaemia (31.7%), gamma-glutamyl transferase increased (26.2%) and blood alkaline phosphatase increased (22.1%). TRAEs leading to drug interruption, dose reduction, and permanent discontinuation occurred in 35 (24.1%), 15 (10.3%), and 3 (2.1%) patients, respectively. Conclusions: Sosimerasib monotherapy has shown promising anti-tumor activity with manageable safety profile in locally advanced/metastatic NSCLC patients harboring KRAS G12C mutation. This study is still ongoing and longer follow-up will provide more solid evidence. Clinical trial information: ChiCTR2200059986 .