D-1553 (garsorasib)，一种对非小细胞肺癌患者的KRASG12C的有效和选择性的抑制剂： I期研究结果

2023-04-06 10:25

D-1553对KRAS G12C突变的NSCLC患者来说是一种很有希望的治疗选择，其安全状况良好，有一定的抗肿瘤活性。

SCI 5 April 2023

D-1553 (garsorasib), a Potent and Selective Inhibitor of KRASG12C in Patients with Non- Small Cell Lung Cancer: Phase I Study Results

（Journal of Thoracic Oncology；IF: 20.121）

Li Z, Song Z, Zhao Y, Wang P, Jiang L, Gong Y, Zhou J, Jian H, Dong X, Zhuang W, Cang S, Yang N, Fang J, Shi J, Lu J, Ma R, Wu P, Zhang Y, Song M, Xu C-W, Shi Z, Zhang L, Wang Y, Wang X, Zhang Y, Lu S

CORRESPONDENCE TO: shunlu@sjtu.edu.cn

Introduction 背景

D-1553 (garsorasib) is a potent and selective oral KRASG12C inhibitor. We report results from a phase I dose-escalation/dose-expansion study of D-1553 in patients with KRAS G12C- mutated NSCLC in multiple sites of China.

D-1553（garsorasib）是一种强效和选择性的口服KRAS G12C抑制剂。我们报告了D-1553在中国多个地区对KRAS G12C突变的NSCLC患者进行的I期剂量递增/剂量扩大研究的结果。

Methods 方法

Patients with KRAS G12C-mutated NSCLC were 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. Safety, pharmacokinetics, and efficacy of D-1553 were evaluated.

KRAS G12C突变的NSCLC患者被给予D-1553 600毫克口服，每天一次，800毫克，每天一次，1200毫克，每天两次，400毫克或600毫克，每天两次的剂量扩大。在剂量扩大中，所有患者都接受600毫克，每天两次。对D-1553的安全性、药代动力学和疗效进行了评估。

Results 结果

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 evaluable for efficacy analysis, 30 patients had partial response (PR) and 38 had stable disease (SD) with a confirmed ORR and DCR of 40.5% and 91.9%, respectively. The median PFS was 8.2 months, and the median DOR was 7.1 months. Among 62 patients evaluable for response at the recommended phase 2 dose (RP2D), PR occurred in 24 patients (ORR, 38.7%) and SD in 32 patients (DCR, 90.3%). The median PFS and DOR were 7.6 months and 6.9 months, respectively. In patients with brain metastasis, ORR and DCR were 17% and 100%, respectively.

在总共79名接受治疗的患者中，75名患者（94.9%）报告了与治疗相关的不良事件，其中30名患者出现了3级或4级事件（38.0%）。大多数的不良事件是可以控制的，患者对研究治疗的耐受性良好。在74名可评估疗效的患者中，30名患者有部分反应（PR），38名患者病情稳定（SD），证实ORR和DCR分别为40.5%和91.9%。中位PFS为8.2个月，中位DOR为7.1个月。在推荐的2期剂量（RP2D）下可评估反应的62名患者中，24名患者出现PR（ORR，38.7%），32名患者出现SD（DCR，90.3%）。中位PFS和DOR分别为7.6个月和6.9个月。在有脑转移的患者中，ORR和DCR分别为17%和100%。

Conclusion 结论

D-1553 represents a promising therapeutic option for patients with KRAS G12C-mutated NSCLC with a well-tolerated safety profile and encouraging anti-tumor activity.

D-1553对KRAS G12C突变的NSCLC患者来说是一种很有希望的治疗选择，其安全状况良好，有一定的抗肿瘤活性。