Article
作者: Shi, Jianhua ; Shi, Zhe ; Xu, Chun-Wei ; Cang, Shundong ; Lu, Shun ; Zhang, Yingqian ; Song, Zhengbo ; Jian, Hong ; Wu, Ping ; Jiang, Liyan ; Zhang, Yiping ; Song, Mengmeng ; Wang, Yaolin ; Li, Ziming ; Wang, Pingli ; Zhuang, Wu ; Lu, Junguo ; Ma, Rui ; Zhou, Jianying ; Wang, Xicheng ; Dong, Xiaorong ; Yang, Nong ; Zhang, Ling ; Gong, Yi ; Zhao, Yanqiu ; Fang, Jian
INTRODUCTION: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.
METHODS: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.
RESULTS: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.
CONCLUSIONS:D-1553 represents a promising therapeutic option for patients with KRAS G12C-mutated NSCLC with a well-tolerated safety profile and encouraging antitumor activity.