GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) for GFH925 (IBI351) and granted GFH925 with Priority Review designation, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation who have received at least one systemic therapy. It’s the first China-developed KRAS G12C inhibitor that has its NDA submission accepted and granted with Priority Review Designation by NMPA. GFH925 also received Breakthrough Therapy Designations this year for treating advanced KRAS G12C-mutant NSCLC patients that have received at least one systemic therapy and colorectal carcinoma (CRC) patients who have received at least two systemic therapies.
The acceptance of NDA submission and Priority Review designation are based on the results from a single-arm registrational Phase II study of GFH925 monotherapy treating advanced KRAS G12C-mutant NSCLC patients who failed or was intolerant of standard-of-care treatment in China (NCT05005234). The results will be presented at the upcoming European Society for Medical Oncology (ESMO) Asia Congress 2023.
The results of GFH925 from a Phase I trial was updated in an oral presentation at the 2023 AACR Annual Meeting. As of data cutoff date (February 10, 2023), of the 67 evaluable NSCLC patients, 41 achieved partial response (PR), with investigator assessed ORR 61.2% and DCR 92.5%. Of 30 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 66.7% (confirmed ORR 53.3%) and DCR 96.7%.
In combating NSCLC, the multi-center trial of GFH925 and ERBITUX® (cetuximab, EGFR inhibitor) has progressed into phase II study in Europe with favorable safety and encouraging efficacy. The trial is led by Professor Rafael Rosell, a world-renowned expert in particular in the field of lung cancer, and partial responses were observed among advanced KRAS G12C-mutant patients. In China, Innovent is also exploring the potential of IBI351(GFH925) in combination therapies for previously untreated advanced NSCLC patients with KRAS G12C mutation; two Phase Ib studies of IBI351（GFH925）in combination with cetuximab and sintilimab (TYVYT®, PD-1 inhibitor) respectively are currently ongoing.
Yu Wang, M.D.,Ph.D.
Chief Medical Officer of GenFleet
“GFH925 is GenFleet’s first NDA-stage product and becomes China’s first KRAS G12C inhibitor that receives NDA acceptance and Priority Review Designation. That demonstrates GFH925’s encouraging safety and efficacy in treating advanced NSCLC, and its potential in commercialization in the future. Meanwhile, GenFleet’s combination study of GFH925 and cetuximab treating NSCLC in 1st line also progressed swiftly in Europe with preliminary results of good safety and efficacy. GenFleet will promote the advancement of more multiple-regional studies in monotherapy and combination therapies and we look forward to positive progress of this study and other studies of GFH925 conducted by Innovent."
Professor Yi-Long Wu
Guangdong Lung Cancer Institute
“KRAS mutation as the ‘undruggable’ target for decades has become one of the most popular directions for clinical development recently. GFH925 is a novel, irreversible covalent inhibitor of KRAS G12C mutation. GFH925 monotherapy demonstrated favorable safety and promising activity in KRAS G12C mutated advanced NSCLC. We look forward to the NDA approval of this novel drug to benefit more NSCLC patients with KRAS G12C mutation soon."
GFH925 is also the first domestic KRAS G12C inhibitor that received CDE Breakthrough Therapy Designation as monotherapy for previously treated KRAS G12C mutant CRC patients. According to the preliminary data of GFH925 monotherapy treating CRC at the 2023 ASCO Annual Meeting, favorable safety/tolerability and promising antitumor activity of GFH925 monotherapy were observed among patients. As of data cutoff date (Feb 16, 2023), a total of 54 metastatic colorectal cancer patients were included for analysis; of 42 evaluable subjects at 600mg BID, ORR was 42.9% (18/42), confirmed ORR was 31.0% (13/42), DCR was 88.1% (37/42).
