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.
GFH547 is developed with novel mechanism of action by reshaping and repurposing intracellular cyclophilin A (CypA) protein to target active RAS proteins across most wild/mutant subtypes. Preclinical data demonstrated profound panRAS inhibitory activity of GFH547 and it holds the potential to overcome adaptive and acquired resistance against SIIP (switch II pocket)-based KRAS inhibitors.
Under the terms of the agreement, GenFleet will conduct an open-label, single-arm and multi-center (10 hospitals in China) study of the combination therapy to evaluate the safety and efficacy among relapsed/refractory DLBCL patients. BeiGene will provide clinical drug supplies of BRUKINSA®(zanubrutinib) for this trial. This study will be the first combination trial conducted by a Chinese biotech to combine CDK9 inhibitor and BTK inhibitor targeting DLBCL.
At present, two phase II studies are actively underway in China and the US, focusing on the treatment of PTCL and AML respectively. A number of subjects in these GFH009 studies have shown partial or complete responses, which underscores the superior safety profile and efficacy of GFH009 in the global arena of CDK9 inhibitor development.
The abstract with results from GFH925 monotherapy treating NSCLC in the registrational phase II study (NCT05005234) was accepted as a LBA (Late-breaking abstracts) program in 2023 ESMO Asia, after the New Drug Application for GFH925 monotherapy treating NSCLC patients was recently accepted by National Medical Products Administration and granted with Priority Review Designation. The data demonstrated encouraging antitumor activity and favorable tolerability of GFH925 among NSCLC patients, with a
