GENFLEET-B(02595): The first patient has been dosed in a phase Ib/II study of the KRAS G12D inhibitor GFH375 in combination with cetuximab or chemotherapy for the treatment of advanced solid tumors.

GENFLEET-B (02595) announced that the first patient in the phase Ib/II study of combined therapy with GFH375 for the treatment of KRAS G12D mutated advanced solid tumors has been enrolled at Peking University Cancer Hospital in Beijing. This study (GFH375X1202) received approval from the National Medical Products Administration in September and includes the combination therapy of GFH375 (an oral KRAS G12D inhibitor) with either cetuximab or chemotherapy; with the GFH375 combined chemotherapy regimen being a first-line treatment for pancreatic ductal adenocarcinoma (PDAC). The phase Ib trial will first be conducted at approximately 15 centers, including Peking University Cancer Hospital. The primary objectives of the overall trial are to assess the safety/tolerability, efficacy, and pharmacokinetic characteristics of GFH375 combined with cetuximab or chemotherapy in solid tumor patients. In the phase II trial, GFH375 combined with chemotherapy (albumin-bound paclitaxel and gemcitabine) will be used to treat first-line advanced PDAC patients, while GFH375 combined with cetuximab (EGFR monoclonal antibody) will be used to treat late-stage PDAC and colorectal cancer (CRC) patients. Dr. Yu Bo Wang, Chief Medical Officer of Jingfang, stated: "We are pleased that the two combination therapy regimens of GFH375 have entered the clinical stage, especially as the first-line treatment for PDAC, which will move GFH375's clinical development from the backline to the frontline. Recent breakthrough study abstracts and oral presentations on the use of GFH375 as a monotherapy for PDAC and non-small cell lung cancer (NSCLC) have demonstrated promising efficacy at ESMO and WCLC, hinting at its potential for treating multiple types of cancer. We look forward to the rapid progress of various domestic and international studies based on this product to benefit patients soon." GFH375 monotherapy was approved to enter the phase I/II trial in June 2024 by the National Medical Products Administration, and GFH375/VS-7375 has been granted Fast Track designation by the FDA this year for the treatment of both first-line and backline in patients with locally advanced or metastatic KRAS G12D mutated PDAC. GFH375 is an oral high-activity, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor, which binds to the KRAS G12D protein in a non-covalent manner, inhibiting its binding with downstream effector proteins, thereby disrupting the sustained activation of the KRAS G12D downstream pathways in cells and effectively inhibiting tumor cell proliferation. Preclinical studies have shown that the inhibitory effect of GFH375 on tumor growth increases with dose and treatment period, with low off-target risks shown in kinase selectivity and safety target tests. Jingfang has reached an agreement with Verastem on the development of three RAS/MAPK-driven cancer products developed by Jingfang. This cooperation grants Verastem exclusive rights to obtain licenses for these three products upon achieving the predetermined milestones in phase I clinical trials. In December 2023, Verastem chose GFH375/VS-7375 (an oral KRAS G12D (ON/OFF) inhibitor) as the lead project for the collaboration, with GFH375 being the first license granted under this collaboration. This license will grant Verastem the development and commercialization rights outside of Greater China, while Jingfang retains these rights within China.