The primary endpoint 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 with KRAS G12C mutation (WJOG14821L).

Abstract

9006 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 not been investigated. Methods: In this single-arm, phase 2 study, chemotherapy-naïve, advanced non-Sq, NSCLC patients with KRAS G12C mutation were enrolled. Participants were treated with sotorasib 960mg, QD plus carboplatin (AUC 5)/pemetrexed 500mg/m2 for four cycles, followed by sotorasib plus pemetrexed until disease progression. The primary endpoint was overall response rate (ORR) by independent review. The secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Using plasma samples, next-generation sequencing analysis was done at baseline, 3 weeks and disease progression. Regarding statistical consideration, the threshold and the expected ORR were set as 40% and 65%, respectively with one-sided α = 0.1, and β = 0.1, the required sample size was 28 cases (Simon’s two-stage design). A total of 30 cases was planned to take into account the possibility of a few dropped or ineligible cases. This study was funded by AMGEN Inc. and Trial identification no. is jRCT2051210086. Results: Between Oct 2021 and Jul 2022, 30 patients were enrolled. Twenty-nine and 27 were analyzed for safety and efficacy, respectively. Of those, median age was 70, male/female: 25/5, never-/smoker: 1/29, ECOG performance status: 0/1 11/19 and PD-L1 expression level: ≥50%/1-49%/<1% 15/10/5. The primary endpoint, ORR by independent review was 88.9% (80%CI 78.5-94.8%). Median PFS was not reached mainly due to shorter follow-up period (median 4.2 months) and PFS rate at 6 months was 61.2%. OS rate at 6 months was 87.0%. Subgroup analysis revealed that ORR did not differ by PD-L1 expression level (≥50%/1-49%/<1%: 76.9%/77.8%/80.0%, respectively). Common adverse events were anemia, neutrophil count decreased, nausea and platelet count decreased. Grade≥3 AEs were mostly hematological toxicities, but one treatment-related death (pneumonia) occurred. At baseline, 70% of plasma samples were positive for KRAS G12C and most common co-occurring mutation was TP53 (50%). At 3 weeks, plasma KRAS G12C disappeared among 60% of patients. Conclusions: Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR and tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. Clinical trial information: jRCT2051210086 .