D-1553 (Garsorasib), a Potent and Selective Inhibitor of KRASG12C in Patients With NSCLC: Phase 1 Study Results

• DOI: 10.1016/j.jtho.2023.03.015
• Publication Date: 2023-03-21T10:19:42Z
• Authors: Ziming Li; Zhengbo Song; Yanqiu Zhao; Pingli Wang; Liyan Jiang; Yi Gong; Jianying Zhou; Hong Jian; Xiaorong Dong; Wu Zhuang; Shundong Cang; Nong Yang; Jian Fang; Jianhua Shi; Junguo Lu; Rui Ma; Ping Wu; Yingqian Zhang; Mengmeng Song; Chun-Wei Xu; Zhe Shi; Ling Zhang; Yaolin Wang; Xicheng Wang; Yiping Zhang; Shun Lu
• Keywords: Proto-Oncogene Proteins p21(ras); Lung Neoplasms; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Mutation; Humans; Protein Kinase Inhibitors

D-1553 (garsorasib) is a potent and selective oral KRASG12C inhibitor. We report results from a phase I dose-escalation and dose-expansion study of D-1553 in patients with KRAS G12C-mutated NSCLC in multiple sites in the People's Republic of China.Patients with KRAS G12C-mutated NSCLC have administrated D-1553 600 mg orally once daily, 800 mg once daily, 1200 mg once daily, 400 mg twice a day, or 600 mg twice a day in dose escalation. In dose-expansion, all patients received 600 mg twice a day. The safety, pharmacokinetics, and efficacy of D-1553 were evaluated.Among a total of 79 treated patients, 75 patients (94.9%) reported treatment-related adverse events with 30 patients experiencing grade 3 or 4 events (38.0%). Most of the adverse events were manageable and the patients tolerated the study treatment well. Among 74 patients assessable for efficacy analysis, 30 patients had a partial response and 38 had stable disease with a confirmed objective response rate (ORR) and disease control rate (DCR) of 40.5% and 91.9%, respectively. The median progression-free survival was 8.2 months, and the median duration of response was 7.1 months. Among 62 patients assessable for response at the recommended phase 2 dose, partial response occurred in 24 patients (ORR, 38.7%) and stable disease in 32 patients (DCR, 90.3%). The median progression-free survival and duration of response were 7.6 months and 6.9 months, respectively. In patients with brain metastasis, ORR and DCR were 17% and 100%, respectively.D-1553 represents a promising therapeutic option for patients with KRAS G12C-mutated NSCLC with a well-tolerated safety profile and encouraging antitumor activity.