Efficacy and safety of glecirasib in solid tumors with KRAS G12C mutation: A pooled analysis of two phase I/II trials

作者：Jian Li, Ting Deng, Yanhong Gu, Antonio Calles, Zhihua Li, Chunmei Bai, Lin Wu, Jing Huang, Xingya Li, Yu Yao, Zhengbo Song, Yongsheng Li, Lian Liu, Ligang Xing, Wenming Wu, Julia Martínez‐Pérez, Ayala Hubert, Jon Zugazagoitia, Jian Zhang, Yongsheng Wang, Yanqiu Zhao, Guilan Wen, Guohao Xia, Diansheng Zhong, Xueqin Chen, Kuirong Jiang, Andrea Wang‐Gillam, Yuli Ding, Sumei Liu, Zhiyue Rao, Xinghu Liu, Lin Shen · 发表于：癌症：英文版 · 年份：2025 · DOI：10.1002/cac2.70056 · 被引用次数：12 · 研究领域：Lung Cancer Treatments and Mutations、Peptidase Inhibition and Analysis、Protease and Inhibitor Mechanisms

BACKGROUND: Glecirasib, an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12 (KRAS G12C), has exhibited clinical activity in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Here, we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma (PDAC) and other solid tumors (excluding NSCLC and CRC) that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited. METHODS: We conducted and analyzed two open-label, phase I/II trials in adult patients with KRAS G12C mutant solid tumors, in which glecirasib was administered orally. The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment. We performed a pooled analysis of all patients, excluding NSCLC and CRC, from both trials. The primary endpoint in the pooled population was objective response rate (ORR). Efficacy and safety were assessed in patients who received at least one dose of glecirasib. RESULTS: As of June 30, 2024, the pooled analysis included 54 patients who were treated with glecirasib: 32 PDACs, 8 biliary tract cancers (BTCs), 4 small intestinal cancers, 3 gastric cancers, 2 appendiceal cancers, and 5 other tumors. At baseline, 24 received ≥ two prior lines of systemic therapy. Of the 53 efficacy-evaluable patients, the confirmed ORR was 50.9% (95% confidence interval [CI], 36.8%-64.9%), with an ORR of 46.9% (95% CI, 29.1%...