GenFleet Therapeutics has announced that its innovative KRAS G12C inhibitor, GFH925, received Priority Review from China's NMPA, a major step for advanced non-small cell lung cancer therapy. This marks a significant milestone toward potential approval for treating advanced non-small cell lung cancer (NSCLC) patients with the KRAS G12C mutation.
In a landmark development for lung cancer treatment, National Medical Products Administration (NMPA), has accepted the New Drug Application (NDA) for GFH925. This is the first time an NDA for a KRAS G12C inhibitor has been accepted in China. The NMPA has also granted GFH925 a priority review designation. Additionally, GFH925 holds Breakthrough Therapy Designations for advanced NSCLC (non-small cell lung cancer) and colorectal carcinoma patients.
NSCLC, accounting for approximately 85% of lung cancer cases, remains a leading cause of cancer-related deaths worldwide. The KRAS G12C mutation, present in a significant subset of NSCLC patients, has been notoriously difficult to target, often leaving affected patients with limited treatment options after first-line therapies fail.
Developed by GenFleet Therapeutics, GFH925 is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by covalently and irreversibly modifying the cysteine residue of the KRAS G12C protein. This innovative approach could potentially lead to new treatment options for patients with specific genetic mutations.
GFH925's journey to this pivotal point began with promising results from a Phase II study, where it was tested as a monotherapy for KRAS G12C-mutant NSCLC patients who had not responded to standard care. The upcoming presentation of these results at the ESMO Asia Congress 2023 is eagerly awaited by the medical community.
The updated results of GFH925 from the phase I study were presented at the 2023 AACR Annual Meeting. As of the data cutoff in February 2023, of the 67 evalsuable NSCLC patients, 41 achieved a partial response (PR), with an investigator-assessed overall response rate (ORR) of 61.2% and a disease control rate (DCR) of 92.5%. Of 30 patients with NSCLC treated at 600mg BID, a better efficacy signal was observed, with an investigator-assessed ORR of 66.7% (confirmed ORR of 53.3%) and a DCR of 96.7%.
In Europe, a significant clinical trial is currently in progress, examining the effects of GFH925 in combination with ERBITUX® (an EGFR inhibitor). This trial has successfully transitioned into its second phase, demonstrating promising outcomes. The combination of these drugs has been shown to be safe and effective. Importantly, partial responses have been observed in patients with advanced KRAS G12C mutations. This study is spearheaded by the globally well-known oncologist, Professor Rafael Rosell.
Dr. Yu Wang, Chief Medical Officer of GenFleet, highlights the significance of GFH925's NDA acceptance and Priority Review Designation, reflecting the drug's promising safety and efficacy profile. This optimism is echoed by Professor Yi-Long Wu from the Guangdong Lung Cancer Institute, who emphasizes the historical challenge of targeting KRAS mutations and the hope GFH925 brings to this field.
Meanwhile, in China, Innovent is investigating the potential of IBI351 (GFH925) in combination therapies for advanced NSCLC patients with the KRAS G12C mutation who have not received prior treatment. Two Phase Ib studies are currently ongoing, testing the combination of IBI351 (GFH925) with cetuximab and sintilimab (a PD-1 inhibitor), respectively.
The acceptance of the NDA for GFH925 by the NMPA is a significant step forward in providing a new treatment option for patients with KRAS G12C mutated NSCLC. The priority review designation will expedite the review process, potentially bringing this much-needed treatment to patients sooner. This development highlights the commitment of GenFleet Therapeutics to bring innovative therapies to patients worldwide.
As GenFleet Therapeutics looks forward to the potential approval of GFH925, it’s clear that this could be a game-changer in the treatment of patients with KRAS G12C-mutated NSCLC, offering new hope for those who have previously had limited treatment options.
