12 June 2024

Garsorasib in patients with KRASG¹²C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial

(Lancet Respir Med;IF:76.2)


  • correspondence to: Prof Shun Lu, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong,University, Shanghai 200030,China,


Background 背景

Garsorasib, a potent KRASG¹²C inhibitor, has shown promising antitumour activity in patients with KRASG¹²C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG¹²C -mutated NSCLC.



Methods 方法

This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRASG¹²C -mutated NSCLC who had previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors from 43 hospitals in China. Participants received 600 mg garsorasib orally twice per day. Tumour assessments were performed at baseline, at the end of every two cycles (of 21 days) for the first eight cycles, and at the end of every three cycles thereafter. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC) following the guidelines in Response Evaluation Criteria in Solid Tumours, version 1.1. Efficacy and safety were assessed in all patients who received at least one dose of garsorasib. This trial is registered at, NCT05383898, and is active but no longer recruiting.

这项开放标签、多中心、单组、2期试验纳入了来自中国43家医院的既往接受过铂类化疗和免疫检查点抑制剂治疗的KRASG¹²C突变NSCLC成人患者。参与者每日2次口服600 mg garsorasib。肿瘤评估在基线时进行,前8个周期每2个周期结束时(21日)进行,之后每3个周期结束时进行。主要终点是由独立审查委员会(IRC)按照《实体瘤疗效评价标准》1.1版的指南评估的客观缓解率(ORR)。我们在接受至少1剂garsorasib治疗的所有患者中评估了疗效和安全性。本试验在ClinicalTrials.gov注册,注册号为NCT05383898,正在进行中,但不再招募。


Findings 结果

From June 17, 2022, to May 17, 2023, of 225 patients screened for eligibility, 123 patients were enrolled and treated with garsorasib. Of these 123 participants, the median age was 64 years (IQR 59–68), 108 (88%) were male and 15 (12%) were female. At data cutoff (Nov 17, 2023), the median follow-up duration was 7·9 months (IQR 6·3–10·4), and 82 (67%) of 123 patients had discontinued treatment. The IRC-confirmed ORR was 50% (61 of 123 patients; 95% CI 41–59). 117 (95%) of 123 patients reported treatment-related adverse events, with 61 (50%) experiencing grade 3 or higher events. The most common types of adverse events of grade 3 or higher associated with garsorasib were hepatic and gastrointestinal events, including increased liver enzymes, such as aspartate aminotransferase (21 [17%] of 123 participants), alanine aminotransferase (19 [15%] of 123 participants), and gamma-glutamyltransferase (28 [23%] of 123 participants); nausea (2 [2%] of 123 participants); and vomiting (2 [2%] of 123 participants). No new safety signals were identified, and most of the adverse events were well managed.

从2022年6月17日至2023年5月17日,在筛选的225例患者中,123例患者被纳入并接受了garsorasib治疗。在这123名参与者中,中位年龄为64岁(IQR 59-68),男性108名(88%),女性15名(12%)。在数据截止日期(2023年11月17日),中位随访时间为7.9个月(IQR 6.3 ~ 10.4), 123例患者中有82例(67%)停止治疗。IRC确认的ORR为50%(61 / 123例患者;95% CI 41-59)。123例患者中有117例(95%)报告了与治疗相关的不良事件,其中61例(50%)发生了3级或更高级别的不良事件。与garsorasib相关的最常见的3级或更高级别不良事件类型包括肝脏和胃肠道事件,包括肝酶升高,例如天冬氨酸转氨酶(123例参与者中的21例[17%])、丙氨酸转氨酶(123例参与者中的19例[15%])和γ -谷氨酰转移酶(123例参与者中的28例[23%])。恶心(123例参与者中的2例[2%]);和呕吐(123例参与者中的2例[2%])。本试验未发现新的安全性信号,大多数不良事件得到了良好管理。


Interpretation 结论

The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG¹²C -mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population.