On June 5th, GenFang Pharmaceuticals announced that GFH375/VS-7375 ( an oral KRAS G12D inhibitor ) received Fast Track Designation (FTD) from the U.S. FDA for the treatment of previously treated patients with unresectable, locally advanced, or metastatic non-small cell lung cancer (NSCLC) with KRAS G12D mutations (concurrent or sequentially treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors) . Previously, GFH375/VS-7375 received another Fast Track Designation from the FDA last year for the treatment of first-line and later-line KRAS G12D -mutant metastatic pancreatic ductal adenocarcinoma (PDAC). Furthermore, GFH375 has already received two Breakthrough Therapy Designations (BTD) in China this year for monotherapy in KRAS G12D -mutant advanced pancreatic cancer and NSCLC.

GFH375 is an orally administered, highly active, and selective small-molecule KRAS G12D (ON/OFF) inhibitor. It binds to the KRAS G12D protein non-covalently, inhibiting its binding to downstream effector proteins, thereby disrupting the sustained activation of downstream pathways by KRAS G12D in cells and ultimately effectively inhibiting tumor cell proliferation. Preclinical studies have shown that the inhibitory effect of GFH375 monotherapy on tumor growth increases with increasing dosage and treatment duration, and it demonstrates low off-target risk in kinase selectivity and safety target assays.

According to a press release from GenFang Pharmaceuticals, GFH375 received clinical trial approval in China in June 2024 and entered a clinical trial as a monotherapy for KRAS G12D- mutant solid tumors. Last year, it entered a registrational Phase 3 clinical trial for an oral KRAS G12D inhibitor (for metastatic pancreatic cancer). Simultaneously, the combination therapy of GFH375 with chemotherapy (for first-line PDAC) or with cetuximab (for PDAC and solid tumors such as colorectal cancer) has entered a Phase 1b/2 trial. Since last year, clinical data on GFH375 monotherapy for PDAC, NSCLC, cholangiocarcinoma, and colorectal cancer has been selected four times for oral presentations or breakthrough study abstracts at the ASCO, WCLC, and ESMO annual meetings, demonstrating the promising efficacy and combination therapy potential of GFH375 across multiple tumor types.

GFH375/VS-7375 entered a Phase 1/2a clinical trial in the United States last year, initiated and advanced by its partner Verastem Oncology. Currently, several international monotherapy and combination therapy trials are underway. Among them, the monotherapy trial for KRAS G12D mutant solid tumors has completed multiple dose level explorations, with no dose-limiting toxicities observed and no drug-related liver function abnormalities reported by evaluable patients.

https://mp.weixin.qq.com/s/3z4jxgtYxciNH2r8RnwBSg