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Clinical Trial
. 2025 Mar;31(3):894-900.
doi: 10.1038/s41591-024-03401-z. Epub 2025 Jan 6.

Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial

Yuankai Shi  1 , Jian Fang  2 , Ligang Xing  3 , Yu Yao  4 , Jian Zhang  5 , Lian Liu  6 , Yongsheng Wang  7 , Changlu Hu  8 , Jianping Xiong  9 , Zhihua Liu  10 , Runxiang Yang  11 , Zhen Wang  12 , Enfeng Zhao  13 , Mengzhao Wang  14 , Yanqiu Zhao  15 , Kejing Tang  16 , Zhihua Li  17 , Zhengbo Song  18 , Yongsheng Li  19 , Wu Zhuang  20 , Bo Jin  21 , Ying Cheng  22 , Yanping Hu  23 , Yanhong Gu  24 , Lin Wu  25 , Rui Ma  26 , Qitao Yu  27 , Yan Yu  28 , Jun Zhao  2 , Hui Zhao  29 , Dongqing Lv  30 , Yanhong Shang  31 , Puyuan Xing  32 , Jin Zhou  33 , Xingya Li  34 , Zhe Liu  35 , Zhaoxia Dai  36 , Guohao Xia  37 , Xueqin Chen  38 , Yi Ba  39 , Chunmei Bai  14 , Qingshan Li  40 , Guangyu An  41 , Weiguo Hu  42 , Yinxiang Wang  43 , Andrea Wang-Gillam  44 , Yuli Ding  43 , Qiao Li  43 , Zhiyue Rao  43
Affiliations
Clinical Trial

Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial

Yuankai Shi et al. Nat Med. 2025 Mar.

Abstract

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRASG12C-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC). Between 15 September 2022 and 28 September 2023, 119 patients with a median age of 62 years were enrolled. As of the data cut-off date on 28 March 2024, the ORR assessed by IRC was 47.9% (56/117; 95% confidence interval: 38.5-57.3%). The incidence of treatment-related adverse events (TRAEs) of any grade was 97.5% (116/119). The incidence of grades 3 and 4 TRAEs was 38.7% (46/119). A total of 5.0% (6/119) of patients discontinued the treatment due to TRAEs. No treatment-related deaths occurred. Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations. ClinicalTrials.gov identifier: NCT05009329 .

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Conflict of interest statement

Competing interests: Y.W., Y.D., Qiao Li and Z.R. are employees of Jacobio Pharmaceuticals. A.W.-G. is an employee of Jacobio (US) Pharmaceuticals. The remaining authors declare no competing interests.

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