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Garsorasib (D-1553) in Combination With Pembrolizumab and Chemotherapy for First-Line Metastatic NSCLC With KRAS G12C Mutation: Results of a Phase 1b Study

Year: 2026

Type: article

Abstract: Background Garsorasib (D-1553) is an orally administered selective KRAS G12C inhibitor. We report results from group 1 of the phase 1b D1553-101 study assessing garsorasib plus pembrolizumab and platinum-based chemotherapy in participants with KRAS G12C‒mutated advanced or metastatic NSCLC. Methods Eligible participants had locally advanced or metastatic NSCLC with KRAS G12C mutation and were candidates for pembrolizumab plus platinum-based chemotherapy. Participants received garsorasib 600 mg once daily (QD) or twice daily (BID) combined with pembrolizumab 200 mg once every 3 weeks plus 4 to 6 cycles of cisplatin or carboplatin and pemetrexed (nonsquamous histology) or carboplatin and paclitaxel (squamous histology). The primary endpoints were safety and incidence of dose-limiting toxicities (DLTs). Results As of February 24, 2024, 17 participants received garsorasib 600 mg QD (n = 10) or BID (n = 7) combined with pembrolizumab plus platinum-based chemotherapy. Overall, 94% of participants experienced grade ≥3 treatment-related adverse events (AEs) and 88% had a dose reduction or interruption due to treatment-related AEs. One participant in the BID group experienced a DLT of grade 2 diarrhea; no other DLTs occurred. Among all participants, the objective response rate was 59% and median progression-free survival was 7.4 months. Conclusion In participants with KRAS G12C‒mutated locally advanced or metastatic NSCLC, despite an encouraging signal of efficacy, the incidence of treatment-related AEs with garsorasib plus pembrolizumab and platinum-based chemotherapy was high, and participants had frequent dose modification or interruption due to treatment-related AEs. Based on these findings, the study did not proceed into phase 2. (NCT04585035)

Source: JTO Clinical and Research Reports

DOI: 10.1016/j.jtocrr.2026.101037