Final analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer KRAS G12C mutation.

8616 Background: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Methods: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Results: Between Oct 2021 and Jul 2022, 30 patients were enrolled and the median follow-up time was 14.8 months (range, 0.6-21.7). The primary endpoint, ORR by independent review was 88.9% (80%CI 78.5-94.8%, 95%CI 70.8-97.6%). Median PFS was 6.6 months (95%CI 5.3-16.7 months) and PFS rate at 12 months was 37.0%. Median time to treatment failure was 7.9 months (95%CI 5.4-13.9 months). Median OS was 20.6 months (95%CI 8.1 moths - not estimated) and OS rate at 12 months was 66.7%. Similar to the initial report, efficacy did not differ by PD-L1 expression level. In patients with PD-L1 expression level ≥50% / 1-49% / < 1%, ORR was 76.9% / 100.0% / 100.0%, and median PFS was 7.6 / 5.7 / 9.7 months, respectively. Common adverse events were anemia, platelet count decreased, neutrophil count decreased, decreased appetite and nausea. Grade≥3 AEs were mostly hematological toxicities, and one treatment-related death (pneumonia) occurred. Twenty-two plasma samples were collected and analyzed using NGS at the time of disease progression. Of those, an increased allele frequency of KRAS G12C was observed in 73% of the patients. TP53 mutation was detected in 55%, and other resistance mechanisms included CDKN2A, BRAF and PIK3CA mutations. Conclusions: Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR with modest PFS and good tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. Clinical trial information: jRCT2051210086 .