Jacobio Pharma (1167.HK) has announced positive results from its Phase II registrational study of glecirasib, a KRAS G12C inhibitor, in patients with previously treated non-small cell lung cancer (NSCLC). The data, presented at the ASCO Plenary Series, highlight the potential of glecirasib as a more effective and safer alternative to chemotherapy in this patient population.
Efficacy and Safety Data
The study revealed a confirmed objective response rate (cORR) of 47.9% (56/117) among second-line NSCLC patients treated with glecirasib monotherapy. This included 4 patients who achieved a complete response (CR) and 36 patients with tumor reduction exceeding 50%. The disease control rate (DCR) was 86.3%.
Median progression-free survival (mPFS) was 8.2 months, and median overall survival (mOS) reached 13.6 months. The median duration of response (mDoR) was not reached, with 6-month and 12-month DOR rates of 73.6% and 56.6%, respectively.
In terms of safety, glecirasib demonstrated a manageable profile. No grade 5 treatment-related adverse events (TRAEs) were observed, and only 5.0% of patients discontinued treatment due to TRAEs. Notably, glecirasib exhibited a favorable gastrointestinal (GI) profile compared to other KRAS G12C inhibitors.
Expert Commentary
Dr. Julia Rotow of the Dana-Farber Cancer Institute commented on the findings, stating, "If glecirasib can match or even bypass current efficacy data with an overall improved side effect profile, this agent would be an attractive treatment option." She further noted that the unique toxicity profile of glecirasib may allow for combinations with agents that are not readily combined with other existing KRAS G12C inhibitors due to overlapping toxicities.
Professor Yuankai Shi, the lead principal investigator of the clinical trial, emphasized the potential of glecirasib to improve outcomes compared to current standard treatments. "Currently, for lung cancer patients harboring the KRAS G12C mutation who fail first-line treatment, chemotherapy such as docetaxel is the main second-line treatment in China. The ORR is 14%, mPFS is 3.0 months, and OS is 9.1 months. Existing clinical data show that glecirasib is more effective and safer than chemotherapy and is expected to bring more treatment options to patients."
Glecirasib in Pancreatic Cancer
Glecirasib has also received orphan drug designation from the FDA for pancreatic cancer and breakthrough therapy designation from China's CDE for second-line or above pancreatic cancer patients with KRAS G12C mutations. Data presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (2024 ASCO GI) showed a cORR of 41.9% (13/31) and a DCR of 93.5% (29/31) in this patient population. The mPFS was 5.6 months, and the mOS was 10.7 months.
Jacobio is currently conducting a registrational pivotal study of glecirasib for pancreatic cancer, with the aim of submitting a New Drug Application (NDA) based on the study results.
