Glecirasib Shows Promise in KRAS G12C-Mutated Pancreatic and Solid Tumors
核心洞察
Glecirasib monotherapy demonstrates a 48% confirmed objective response rate (cORR) and a 90% disease control rate (DCR) in patients with KRAS G12C (搜索)-mutated solid tumors (搜索).
In second-line and above pancreatic cancer (搜索) patients with KRAS G12C (搜索) mutation, glecirasib achieved a 41.9% cORR and a 93.5% DCR, with median overall survival of 10.7 months.
Glecirasib exhibits good tolerability, with mostly grade 1-2 treatment-related adverse events and only 25% of patients experiencing grade 3 or above TRAEs.
Jacobio Pharma (搜索) presented data on glecirasib, a KRAS G12C (搜索) inhibitor, at the 2024 ASCO Gastrointestinal Cancers Symposium, showcasing its potential in treating pancreatic cancer (搜索) and other solid tumors (搜索) harboring the KRAS G12C mutation. The global study enrolled 52 patients across multiple regions, including 31 with pancreatic cancer and 21 with other solid tumors.
Efficacy in Pancreatic Cancer and Other Solid Tumors
The data, as of December 6, 2023, revealed that among 50 evaluable patients with solid tumors (搜索), glecirasib monotherapy achieved a confirmed objective response rate (cORR) of 48% (24/50) and a disease control rate (DCR) of 90% (45/50). Specifically, in second-line and above KRAS G12C (搜索) mutated pancreatic cancer (搜索) patients, the cORR was 41.9% (13/31), and the DCR was 93.5% (29/31). The median progression-free survival (mPFS) was 5.6 months, and the median overall survival (mOS) was 10.7 months. In other solid tumor patients, the cORR was 57.9% (11/19), DCR was 84.2% (16/19), and the mPFS was 7.0 months, with the mOS data still maturing.
Safety and Tolerability
Glecirasib demonstrated favorable tolerability and safety profiles. The majority of treatment-related adverse events (TRAEs) were grades 1-2, with grade 3 or above TRAEs occurring in 25% of patients. Importantly, no patient permanently withdrew from the study due to TRAEs.
Expert Commentary
Professor Lin Shen, director of the Peking University Cancer Hospital gastroenterology department and principal investigator for the trial, noted, "Pancreatic cancer (搜索) is a highly malignant tumor, and current patients lack effective standardized treatment methods, with a five-year overall survival rate of only 5%. The clinical data of glecirasib have preliminarily confirmed the efficacy in patients with pancreatic cancer and other solid tumors (搜索). Compared with the standard chemotherapy treatment, the ORR of glecirasib is higher, and the safety and tolerance is better."
Regulatory and Clinical Development
Glecirasib has been granted breakthrough therapy designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China for pancreatic cancer (搜索) patients with KRAS G12C (搜索) mutation who have progressed after frontline standard care. A registrational pivotal study for pancreatic cancer, the first global pancreatic cancer KRAS G12C registrational clinical study, was approved by CDE in July 2023. The results will support a New Drug Application (NDA) for pancreatic cancer.