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Cited by 49Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentProtein Kinase Regulation and GTPase Signaling

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

Li, Ziming, Dang, Xiaomin, Huang, Dingzhi, Jin, Shi, Li, Weiwei, Shi, Jianhua, Wang, Xicheng, Zhang, Yiping +68 more·2024·The Lancet Respiratory Medicine
DOI 10.1016/s2213-2600(24)00110-3
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Abstract

Background Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRAS G12C inhibitor, has shown promising antitumour activity in patients with KRAS G12C-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 KRAS G12C-mutated NSCLC.Methods This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRAS G12C-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 ClinicalTrials.gov, NCT05383898, and is active but no longer recruiting.Findings 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.Interpretation 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 KRAS G12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population.Funding InventisBio.

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Authors
Li, Z., Dang, X., Huang, D., Jin, S., Li, W., Shi, J., Wang, X., Zhang, Y., Song, Z., Zhang, J., Zhuang, W., Liu, X., Jiang, L., Meng, X., Zhao, M., Zhou, J., Zhang, L., Wang, P., Luo, H., Yang, J., Cang, S., Wang, X., Zhang, L., Lu, S., Li, Z., Dang, X., Huang, D., Jin, S., Li, W., Shi, J., Wang, X., Zhang, Y., Song, Z., Zhang, J., Zhuang, W., Liu, X., Jiang, L., Meng, X., Zhao, M., Zhou, J., Zhang, L., Wang, P., Luo, H., Yang, J., Cang, S., Wang, X., Wang, J., Cui, J., Yu, Y., Zhang, Z., Lu, J., Yang, W., Li, G., Feng, J., Lv, D., Wu, L., Fang, Y., Wang, Y., Zhao, Y., Cao, B., Zhu, W., Zhuang, Z., Li, Q., Wang, M., Zhou, H., Dong, X., Hu, S., Fang, J., Xu, C.-W., Zhang, Y., Wang, W., Xiang, Z., Shi, Z., Wang, Y., Zhang, L., & Lu, S.
Affiliations
  • Xuzhou Central Hospital (CN)
  • InventisBio Co., Ltd. (China) (CN)
  • Shanghai Jiao Tong University (CN)
  • Fujian Provincial Cancer Hospital (CN)
  • First Hospital of China Medical University (CN)
  • First Affiliated Hospital Zhejiang University (CN)
  • Henan Provincial People's Hospital (CN)
  • Third Xiangya Hospital (CN)
  • Zhejiang Cancer Hospital (CN)
ORCID
Venue
The Lancet Respiratory Medicine
Publisher
Elsevier BV
Published
2024-08
Volume
12
Issue
8
Pages
589-598
ISSN
2213-2600 (ISSN-L)
DOI
10.1016/s2213-2600(24)00110-3
OpenAlex
W4399477559
Cited by
49
References
28
Citations by year
2026: 25 · 2025: 22 · 2024: 2
FWCI
14.23
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Lancet Respiratory Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
KRAS G12C inhibitors, metastatic lung cancer, locally advanced lung cancer, objective response rate, progression-free survival, treatment safety, adverse events, real-world experience, platinum-based chemotherapy, immune checkpoint inhibitors, treatment discontinuation
MeSH terms
Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, China, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Proto-Oncogene Proteins p21(ras), Treatment Outcome

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