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

Yuankai Shi; Jian Fang; Ligang Xing; Yu Yao; Jian Zhang; Lian Liu; Yongsheng Wang; Changlu Hu; Jianping Xiong; Zhihua Liu; Runxiang Yang; Zhen Wang; Enfeng Zhao; Mengzhao Wang; Yanqiu Zhao; Kejing Tang; Zhihua Li; Zhengbo Song; Yongsheng Li; Wu Zhuang; Bo Jin; Ying Cheng; Yanping Hu; Yanhong Gu; Lin Wu; Rui Ma; Qitao Yu; Yan Yu; Jun Zhao; Hui Zhao; Dongqing Lv; Yanhong Shang; Puyuan Xing; Jin Zhou; Xingya Li; Zhe Liu; Zhaoxia Dai; Guohao Xia; Xueqin Chen; Yi Ba; Chunmei Bai; Qingshan Li; Guangyu An; Weiguo Hu; Yinxiang Wang; Andrea Wang-Gillam; Yuli Ding; Qiao Li; Zhiyue Rao

doi:10.1038/s41591-024-03401-z

Glecirasib in KRAS^G12C-mutated nonsmall-cell lung cancer: a phase 2b trial

Yuankai Shi, Jian Fang, Ligang Xing, Yu Yao, Jian Zhang, Lian Liu, Yongsheng Wang, Changlu Hu, Jianping Xiong, Zhihua Liu, Runxiang Yang, Zhen Wang, Enfeng Zhao, Mengzhao Wang, Yanqiu Zhao, Kejing Tang, Zhihua Li, Zhengbo Song, Yongsheng Li, Wu ZhuangBo Jin, Ying Cheng, Yanping Hu, Yanhong Gu, Lin Wu, Rui Ma, Qitao Yu, Yan Yu, Jun Zhao, Hui Zhao, Dongqing Lv, Yanhong Shang, Puyuan Xing, Jin Zhou, Xingya Li, Zhe Liu, Zhaoxia Dai, Guohao Xia, Xueqin Chen, Yi Ba, Chunmei Bai, Qingshan Li, Guangyu An, Weiguo Hu, Yinxiang Wang, Andrea Wang-Gillam, Yuli Ding, Qiao Li, Zhiyue Rao

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6 Scopus citations

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 KRAS^G12C-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.

Original language	English
Article number	193
Pages (from-to)	894-900
Number of pages	7
Journal	Nature medicine
Volume	31
Issue number	3
DOIs	https://doi.org/10.1038/s41591-024-03401-z
State	Published - Mar 2025

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@article{59081da5dff744a3a24461e92fb7eabb,

title = "Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer: a phase 2b trial",

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.",

author = "Yuankai Shi and Jian Fang and Ligang Xing and Yu Yao and Jian Zhang and Lian Liu and Yongsheng Wang and Changlu Hu and Jianping Xiong and Zhihua Liu and Runxiang Yang and Zhen Wang and Enfeng Zhao and Mengzhao Wang and Yanqiu Zhao and Kejing Tang and Zhihua Li and Zhengbo Song and Yongsheng Li and Wu Zhuang and Bo Jin and Ying Cheng and Yanping Hu and Yanhong Gu and Lin Wu and Rui Ma and Qitao Yu and Yan Yu and Jun Zhao and Hui Zhao and Dongqing Lv and Yanhong Shang and Puyuan Xing and Jin Zhou and Xingya Li and Zhe Liu and Zhaoxia Dai and Guohao Xia and Xueqin Chen and Yi Ba and Chunmei Bai and Qingshan Li and Guangyu An and Weiguo Hu and Yinxiang Wang and Andrea Wang-Gillam and Yuli Ding and Qiao Li and Zhiyue Rao",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.",

year = "2025",

month = mar,

doi = "10.1038/s41591-024-03401-z",

language = "English",

volume = "31",

pages = "894--900",

journal = "Nature medicine",

issn = "1078-8956",

number = "3",

}

Shi, Y, Fang, J, Xing, L, Yao, Y, Zhang, J, Liu, L, Wang, Y, Hu, C, Xiong, J, Liu, Z, Yang, R, Wang, Z, Zhao, E, Wang, M, Zhao, Y, Tang, K, Li, Z, Song, Z, Li, Y, Zhuang, W, Jin, B, Cheng, Y, Hu, Y, Gu, Y, Wu, L, Ma, R, Yu, Q, Yu, Y, Zhao, J, Zhao, H, Lv, D, Shang, Y, Xing, P, Zhou, J, Li, X, Liu, Z, Dai, Z, Xia, G, Chen, X, Ba, Y, Bai, C, Li, Q, An, G, Hu, W, Wang, Y, Wang-Gillam, A, Ding, Y, Li, Q & Rao, Z 2025, 'Glecirasib in KRAS^G12C-mutated nonsmall-cell lung cancer: a phase 2b trial', Nature medicine, vol. 31, no. 3, 193, pp. 894-900. https://doi.org/10.1038/s41591-024-03401-z

TY - JOUR

T1 - Glecirasib in KRASG12C-mutated nonsmall-cell lung cancer

T2 - a phase 2b trial

AU - Shi, Yuankai

AU - Fang, Jian

AU - Xing, Ligang

AU - Yao, Yu

AU - Zhang, Jian

AU - Liu, Lian

AU - Wang, Yongsheng

AU - Hu, Changlu

AU - Xiong, Jianping

AU - Liu, Zhihua

AU - Yang, Runxiang

AU - Wang, Zhen

AU - Zhao, Enfeng

AU - Wang, Mengzhao

AU - Zhao, Yanqiu

AU - Tang, Kejing

AU - Li, Zhihua

AU - Song, Zhengbo

AU - Li, Yongsheng

AU - Zhuang, Wu

AU - Jin, Bo

AU - Cheng, Ying

AU - Hu, Yanping

AU - Gu, Yanhong

AU - Wu, Lin

AU - Ma, Rui

AU - Yu, Qitao

AU - Yu, Yan

AU - Zhao, Jun

AU - Zhao, Hui

AU - Lv, Dongqing

AU - Shang, Yanhong

AU - Xing, Puyuan

AU - Zhou, Jin

AU - Li, Xingya

AU - Liu, Zhe

AU - Dai, Zhaoxia

AU - Xia, Guohao

AU - Chen, Xueqin

AU - Ba, Yi

AU - Bai, Chunmei

AU - Li, Qingshan

AU - An, Guangyu

AU - Hu, Weiguo

AU - Wang, Yinxiang

AU - Wang-Gillam, Andrea

AU - Ding, Yuli

AU - Li, Qiao

AU - Rao, Zhiyue

PY - 2025/3

Y1 - 2025/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85214088954&partnerID=8YFLogxK

U2 - 10.1038/s41591-024-03401-z

DO - 10.1038/s41591-024-03401-z

M3 - Article

C2 - 39762419

AN - SCOPUS:85214088954

SN - 1078-8956

VL - 31

SP - 894

EP - 900

JO - Nature medicine

JF - Nature medicine

IS - 3

M1 - 193

ER -

Glecirasib in KRAS^G12C-mutated nonsmall-cell lung cancer: a phase 2b trial

Abstract

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