GenFleet Therapeutics announced that oral KRAS G12D (ON/OFF) inhibitor GFH375 has been granted with the Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), for treatment of KRAS G12D-mutant non-small cell lung cancer (NSCLC) patients who have received at least one prior systemic therapy.
This designation is supported by the phase I/II data from the GFH375X1101 study, demonstrating GFH375's best‑in‑class monotherapy efficacy and manageable safety/tolerability for NSCLC in the global KRAS G12D inhibitor landscape. The preliminary data from GFH375 monotherapy treating KRAS G12D-mutant patients with solid tumors and NSCLC were featured in late-breaking abstract (LBA) and oral presentation at the 2025 American Society of Clinical Oncology Annual Meeting and the 2025 World Conference on Lung Cancer. More updated study data are expected to be published at global academic events later this year.
“GenFleet has established its integrated R&D capabilities in the program of fulzerasib, a marketed KRAS G12C inhibitor. Globally, no targeted therapies for KRAS G12D mutation have yet been approved, representing a significant unmet medical need across major tumor types carrying the G12D mutation. Within the global landscape of KRAS G12D inhibitor clinical development, GFH375 is progressing at the fastest pace for NSCLC treatment, showing encouraging efficacy and a manageable safety profile. Given its favorable monotherapy druggability and efficacy, GFH375 holds promising clinical potential as a single agent and in combination regimens. ”Prof. Shun Lu, stated Shanghai Chest Hospital.
"We are deeply impressed by the urgent need for targeted therapies among patients harboring KRAS G12D mutation. We are encouraged by GFH375's robust efficacy in the study and hope the BTD granted by CDE helps to accelerate the development and the ultimate launch of GFH375 to benefit patients. The extensive clinical program for GFH375/VS‑7375, in China by GenFleet and outside of China by its partner Verastem Oncology, underscores its broad therapeutic potential across multiple major tumor types. We look forward to presenting updated data for GFH375 in various indications at global academic events later this year.”stated Yu Wang, M.D., Ph.D.,Chief Medical Officer of GenFleet.
GFH375 obtained clinical trial approval for a phase I/II study in China in June 2024. Currently, GFH375 monotherapy for metastatic pancreatic cancer has advanced into the world's first phase III trial of an oral KRAS G12D inhibitor; besides, GFH375/VS-7375 has been granted with the U.S. FDA Fast Track Designation for the treatment of metastatic KRAS G12D-mutated pancreatic ductal adenocarcinoma (PDAC) across all lines of therapy. Multiple monotherapy and combination trials of GFH375/VS-7375 for different tumor types are advancing smoothly, including the GenFleet-initiated phase Ib/II trial of GFH375 combined with chemotherapy (AG）as first-line treatment for PDAC.
