FDA Approves Phase III Trial for GenFleet's GFH925 in Metastatic CRC

GenFleet Therapeutics, a biotech firm at the forefront of oncology and immunology, has received the green light from the US FDA to proceed with a pivotal phase III clinical trial for its GFH925 drug, a KRAS G12C inhibitor. This marks a significant milestone as it is the inaugural phase III study globally to focus on KRAS G12C inhibitor monotherapy for colorectal cancer (CRC) patients who have become resistant to standard treatments.

GFH925 has already garnered Breakthrough Therapy Designation from China's NMPA for its potential in treating advanced CRC that has not responded to prior treatments. Additionally, it has been granted similar status for non-small cell lung cancer (NSCLC) patients with the G12C mutation. The upcoming trial, known as GFH925X0301, will involve participants with KRAS G12C mutations who have seen their disease progress despite multiple treatment attempts or who could not tolerate their last treatment.

The primary goal of the trial is to evaluate the effectiveness of GFH925 against the existing standard of care. Early studies have shown that GFH925's monotherapy for CRC has a superior objective response rate and median progression-free survival compared to other single-agent KRAS G12C inhibitors. It also matches the efficacy of combination treatments involving other G12C inhibitors and anti-EGFR antibodies.

Yu Wang, GenFleet's Chief Medical Official, expressed gratitude for the FDA's acknowledgment of GFH925's efficacy and safety, highlighting the importance of this trial for advanced CRC treatment. The company is optimistic about the drug's potential as a front-line treatment for CRC in the future.

CRC is a significant global health concern, with the GLOBOCAN 2022 report indicating over 1.9 million new cases and nearly 900,000 deaths annually. KRAS mutations are prevalent in approximately 40% of CRC patients, making it a critical target for innovative treatments. Standard treatments for CRC that has spread to other organs typically involve combinations of chemotherapy drugs and targeted therapies.

The presence of the KRAS mutation in CRC is linked to a more severe disease status, poor tumor differentiation, and a worse prognosis. Despite the availability of checkpoint inhibitors for some cancer types, their use in CRC is limited, indicating a need for safer and more targeted therapies. Furthermore, the use of EGFR inhibitors can lead to secondary KRAS mutations, further complicating treatment.

GFH925 is a first-of-its-kind KRAS G12C inhibitor developed in China, which has shown promising results in phase I studies, with an objective response rate of 45.8% and a disease control rate of 89.6% in patients receiving 600mg twice daily. The median progression-free survival for these patients was 7.6 months. The drug works by irreversibly targeting the G12C mutation, inhibiting the downstream signaling pathways that promote tumor growth.

RAS proteins, including KRAS, are implicated in various cancers, with KRAS mutations being particularly common in pancreatic, colon, and lung cancers. GFH925's high selectivity for the G12C mutation could offer a significant advantage in treating these cancers, providing a much-needed treatment option for patients with limited therapeutic alternatives.