This multi-center, open-label (~20 sites in China) trial enrolls patients with advanced G12D-mutant solid tumors, including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC)—three cancer types with high prevalence of G12D mutations
Fulzerasib (GFH925/IBI351) received approval in China on Aug. 21 for the treatment of adult patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. The first hospital prescription was issued on Aug. 31 and the medications were already shipped to chain pharmacies across the country.
The NDA approval is based on the results from a single-arm registrational study (NCT05005234) intended to evaluate the efficacy and safety of fulzerasib monotherapy in advanced NSCLC patients with KRAS G12C mutation who failed or were intolerant to the standard treatment in China. The updated data from this registration study has been published in full manuscript in the Journal of Thoracic Oncology (JTO) and selected for oral presentation at the 2024 World Conference on Lung Cancer (WCLC) .
GFH375 was selected as Verastem’s lead discovery program from its collaboration with GenFleet established in 2023. GFH375/VS-7375 is an oral, potent and selective KRAS G12D dual inhibitor of ON (GTP) and OFF (GDP) states.
GFH375 is a highly potent and selective KRAS G12D inhibitor targeting both "ON" (GTP-bound) and "OFF" (GDP-bound) states of the protein. According to the latest preclinical findings posted at 2024 AACR annual meeting, GFH375 demonstrated preliminary safety data, favorable oral bioavailability and potent efficacy across preclinical models; moreover, GFH375 holds the potential for treating G12D-mutant cancers with brain metastases.
The preliminary result of the trial was accepted as a late-breaking abstract and selected for oral presentation at the clinical science symposium of lung cancer treatment, highlighting the combination therapy's promising efficacy and its excellent safety/tolerability profile. Notably, this marks the first time that a KRAS G12C inhibitor is combined with an EGFR inhibitor as a first-line NSCLC treatment with its data presented at a global academic event.
It is the first phase III trial of KRAS G12C inhibitor monotherapy targeting CRC patients worldwide, with GFH925 being the first G12C inhibitor that received Breakthrough Therapy Designation (BTD) from China's National Medical Products Administration (NMPA) for previously treated advanced CRC. GFH925 was also granted BTD and New Drug Application acceptance with Priority Review Designation by NMPA for previously treated advanced non-small cell lung cancer（NSCLC）patients with G12C mutation.
GFH375 is a highly potent and selective KRAS G12D inhibitor targeting both "ON" (GTP-bound) and "OFF" (GDP-bound) states of the protein. With preliminary safety data, favorable oral bioavailability and potent efficacy across preclinical models, GFH375 also holds the potential for treating KRAS G12D mutant cancers with brain metastases.
