GENFLEET-B(02595): GFH375 (an oral KRAS G12D inhibitor) has entered a Phase II study for first-line treatment of non-small cell lung cancer, which will explore multiple treatment regimens including monotherapy, combination with EGFR monoclonal antibodies, or chemotherapy.

GENFLEET-B (02595) announced that GFH375 has entered a Phase II study as a first-line treatment for KRAS G12D mutant advanced non-small cell lung cancer (NSCLC), which includes monotherapy, combination therapy with EGFR monoclonal antibody (cetuximab), or combination chemotherapy (pemetrexed). This multicenter, open-label, randomized clinical study will take place at dozens of research centers across the country, with Guangdong Provincial People's Hospital as the leading center. GFH375/VS-7375 is the first KRAS G12D inhibitor in China to receive Breakthrough Therapy Designation (BTD) for NSCLC and has also obtained Fast Track Designation (FTD) from the U.S. FDA for the treatment of locally advanced unresectable or metastatic NSCLC harboring KRAS G12D mutations. Currently, the first-line standard treatment for KRAS G12D mutant patients is based on driver gene-negative NSCLC, but the survival benefit is limited, and there are even fewer effective subsequent treatment options after first-line resistance. Additionally, multiple real-world studies show that patients with KRAS G12D mutant NSCLC have a poorer overall prognosis when receiving first-line chemotherapy immunotherapy compared to KRAS wild-type or non-KRAS G12D mutant patients. GFH375 has entered the world's first registrational Phase III study for the treatment of NSCLC with an oral KRAS G12D inhibitor and has demonstrated best-in-class efficacy in previously published data on KRAS G12D inhibitors used as monotherapy for NSCLC. Updated data from the Phase I/II trial of GFH375 monotherapy for NSCLC (abstract number 2333) has been confirmed for an oral presentation at this year's World Lung Cancer Conference (WCLC) in Seoul, which will be announced on September 14 during the session Beyond KRAS: Emerging Targets, Smart Therapies. At the level of combination therapy, preclinical research presented at this year's American Association for Cancer Research (AACR) annual meeting showed that GFH375 in combination with cetuximab produced a significant tumor suppression effect in a KRAS G12D mutant NSCLC animal model, exceeding the effects of either monotherapy. Additionally, GFH375 entered into Ib/II clinical trials for combination chemotherapy or cetuximab treatment of various solid tumors last year, showing preliminary good safety/tolerability without observed significant toxicity overlap; the research data on GFH375 combined with cetuximab for RAS mutant solid tumors has been fully submitted for abstract presentation at this year's European Society for Medical Oncology (ESMO) annual meeting. Dr. Yu Wang, Chief Medical Officer of Jinfoang, stated: Based on the clinical efficacy of GFH375 in NSCLC monotherapy and the positive advancement of several combination therapy studies, we are confident in pushing the GFH375 lung cancer therapy from the later lines to the front line. Over the past two years, multiple clinical programs for GFH375 have been efficiently advanced, and clinical data for GFH375 treating multiple tumor types continues to be featured in international academic conferences as LBAs or oral presentations; at the same time, we deeply feel the urgent need for innovative targeted drugs among KRAS G12D mutant patients and look forward to more innovative therapies from other companies benefiting these patients. GFH375 is an orally administered, highly active, and highly selective small molecule KRAS G12D (ON/OFF) inhibitor. It binds non-covalently to the KRAS G12D protein, inhibiting its interaction with downstream effector proteins, thereby disrupting the sustained activation of downstream pathways by KRAS G12D within cells, ultimately leading to a highly effective suppression of tumor cell proliferation. Preclinical studies have shown that the tumor growth inhibition effect of GFH375 monotherapy increases with dosage and duration of administration, and it has demonstrated low off-target risk in kinase selectivity and safety target tests. Jinfoang has reached a licensing and early collaboration agreement with Verastem Oncology (Verastem) regarding three products developed by Jinfoang for RAS/MAPK driven cancers. This collaboration grants Verastem exclusive options to obtain licenses for these three products after successfully reaching predefined milestones in Phase I clinical trials. In December 2023, Verastem selected GFH375/VS-7375 as its lead project in this collaboration and licensed GFH375 in January 2025, marking it as the first license arising from this collaboration framework. This license will grant Verastem development and commercialization rights outside of China, while Jinfoang retains rights within China.