GenFleet Announces Approval of KRAS G12C Inhibitor for Advanced Lung Cancer Treatment
Saturday, August 24, 2024
GenFleet Therapeutics has announced that China's National Medical Products Administration (NMPA) has approved Dupert® (fulzerasib, GFH925/IBI351) for treating patients with advanced non-small cell lung cancer (NSCLC) with the KRAS G12C mutation who have undergone at least one systemic therapy.
The RAS protein family includes KRAS, HRAS, and NRAS, with KRAS mutations found in nearly 90% of pancreatic cancers, 30-40% of colon cancers, and 15-20% of lung cancers. The KRAS G12C mutation is more common than other mutations like ALK, ROS1, RET, and NTRK.
Fulzerasib is the first KRAS G12C inhibitor developed in China, with its New Drug Application (NDA) accepted under Priority Review in 2023. The drug has also received two Breakthrough Therapy Designations for advanced KRAS G12C-mutant NSCLC and colorectal cancer (CRC).
Fulzerasib (GFH925/IBI351), developed by GenFleet Therapeutics, is an oral KRAS G12C inhibitor designed to block the GTP/GDP exchange, a crucial step in cancer pathway activation, by irreversibly modifying the KRAS G12C protein. Preclinical studies have shown that GFH925 selectively targets the G12C mutation, effectively inducing tumor cell death and halting cell growth.
The approval is based on a single-arm study (NCT05005234) that evaluated the efficacy and safety of fulzerasib monotherapy in patients with advanced NSCLC with the KRAS G12C mutation who had not responded to standard treatment. Results from this study were published in the Journal of Thoracic Oncology (JTO) and presented at the 2024 World Conference on Lung Cancer (WCLC).
As of December 13, 2023, 116 NSCLC patients were enrolled in the study, showing promising antitumor activity and good tolerance. The objective response rate (ORR) was 49.1%, and the disease control rate (DCR) was 90.5%. The median progression-free survival (PFS) was 9.7 months, while the median overall survival (OS) has not yet been reached.
NSCLC accounts for about 85% of all lung cancer cases, with KRAS being the most frequently mutated gene in these patients. KRAS mutations often don't respond well to approved therapies targeting EGFR or ALK, leaving limited treatment options after the first-line standard of care.
GenFleet is also exploring the potential of fulzerasib in combination with other therapies. In 2023, they began a first-line NSCLC study (KROCUS) in Europe, combining fulzerasib with cetuximab, led by Professor Rafael Rosell. Early phase II results from this study showed an ORR of 81.8% and a DCR of 100%, with notable efficacy in patients with brain metastases.
The rapid development of fulzerasib, its approval in China, and the collaboration with Innovent Biologics. The KROCUS study in Europe is showing promising results, potentially offering a new first-line treatment option for G12C-mutated NSCLC patients.
in terms of ORR and PFS. The FDA has approved a phase III study of fulzerasib for treating G12C-mutated refractory, metastatic CRC. Fulzerasib is also the first G12C inhibitor to receive Breakthrough Therapy Designation for CRC treatment in China.
In September 2021, Innovent and GenFleet entered an exclusive agreement to develop and commercialise GFH925 in China, with an option for global expansion. The NMPA granted Breakthrough Therapy
Designation for fulzerasib in January 2023 for advanced NSCLC and in May 2023 for advanced CRC. In August 2024, the NMPA approved fulzerasib for treating advanced NSCLC with the KRAS G12C mutation.
Source: genfleet.com
