Beijing, Shanghai & Boston, Aug 7, 2024 — Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, today announced that it has completed the first patient dosage in the Phase III clinical trial of KRAS G12C inhibitor glecirasib in combination with the SHP2 inhibitor JAB-3312 versus standard care (chemotherapy plus anti-PD-1 antibody) in front-line KRAS G12C mutant non-small cell lung cancer (NSCLC). JAB-3312 is the first SHP2 inhibitor that entered a registration clinical trial globally.

The new drug application (NDA) of glecirasib monotherapy for second-line and beyond NSCLC with KRAS G12C mutation was granted Priority Review designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China on May 21, 2024. 

Andrea Gillam-Wang M.D., Ph.D., Chief Medical Officer and Head of Global R&D at Jacobio, said: "Currently, global developers of KRAS G12C inhibitors are exploring how to use combination therapy to bring better efficacy and sequential treatment plans to patients. According to previous studies, SHP2, as a sensitizer on the tumor immune pathway, can synergistically kill tumors with KRAS G12C. We hope to replace the standard treatment consisting of multiple intravenous drugs through this trial."

According to data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024, glecirasib in combination with JAB-3312 resulted confirmed objective response rate (cORR) of 64.7% (66/102) and preliminary median progression-free survival (mPFS) of 12.2 months in the front-line NSCLC. The optimal dosing schedule Glecirasib at 800mg daily combined with JAB-3312 at 2mg daily one week on and one week off resulted a cORR of 77.4% (24/31), and 54.8% (17/31) of patients achieved a deep response with tumors shrinking by more than 50%. Regarding on the safety data from all study patients the incidence of grade 3 or 4 treatment-related adverse events (TRAE) was 43.8%, and there was no treatment-related death. The overall safety is manageable.

About Glecirasib
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include a pivotal clinical trial in NSCLC in China, combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with cetuximab in colorectal cancer, and a registrational pivotal clinical trial of single agent for pancreatic cancer. The pancreatic cancer indication has obtained orphan drug designation in the United States and breakthrough therapy designation in China.

About JAB-3312
JAB-3312 is a highly selective SHP2 allosteric inhibitor with the best-in-class potential. Jacobio is currently conducting multiple clinical trials of JAB-3312 in China, the United States and Europe, including the combination therapy trial with glecirasib. The Phase III study in combination with KRAS G12C inhibitor glecirasib has been approved in China in February 2024.

About Jacobio