GENFLEET-B (02595) announced that the first patient has been dosed in the Ib/II study of GFH375, a KRAS G12D inhibitor, in combination with therapies targeting advanced solid tumors with KRAS G12D mutations, at Peking University Cancer Hospital. The study (GFH375X1202) received approval from the National Medical Products Administration for clinical trials in September and includes two combined therapy regimens: GFH375 (an oral KRAS G12D inhibitor) paired with either cetuximab or chemotherapy, with the chemotherapy regimen focusing on first-line treatment for pancreatic ductal adenocarcinoma (PDAC). The Phase Ib trial will initially take place at about 15 centers, including Peking University Cancer Hospital, with the main objectives to evaluate the safety, tolerability, efficacy, and pharmacokinetic profiles of both combinations in solid tumor patients. In Phase II, the GFH375 plus chemotherapy regimen (albumin-bound paclitaxel and gemcitabine) will treat first-line advanced PDAC patients, while the GFH375 combined with cetuximab (an EGFR antibody) will target patients with advanced PDAC and colorectal cancer (CRC). Dr. Yu Wang, Chief Medical Officer of GENFLEET, expressed his excitement that both combination therapies for GFH375 have entered the clinical stage, particularly highlighting the progression of GFH375 in clinical development for first-line PDAC treatment. Recent data on GFH375 monotherapy for PDAC and non-small cell lung cancer (NSCLC) were presented as breakthrough abstracts and oral reports at ESMO and WCLC, demonstrating promising efficacy in treating multiple tumor types. GENFLEET looks forward to accelerating the advancement of multiple domestic and international studies based on this product for the benefit of patients. The GFH375 monotherapy was granted approval for the I/II trial by the National Medical Products Administration in June 2024, and GFH375/VS-7375 has received FDA Fast Track designation this year for use in first-line and later-line treatment of locally advanced, metastatic KRAS G12D mutant PDAC patients. GFH375 is a highly active and selective oral small molecule KRAS G12D (ON/OFF) inhibitor that 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 and effectively suppressing tumor cell proliferation. Preclinical studies have shown that the inhibitory effect of GFH375 on tumor growth increases with the dosing schedule and amount, demonstrating low off-target risk in enzyme selectivity and safety assessments. GENFLEET has established a licensing and early collaboration agreement with Verastem for three products related to RAS/MAPK driven cancers developed by GENFLEET. This collaboration grants Verastem exclusive options to obtain licenses for these three products upon successfully reaching predetermined milestones in the Phase I clinical trials. In December 2023, Verastem selected GFH375/VS-7375 (an oral KRAS G12D (ON/OFF) inhibitor) as the lead project in their collaboration, marking the first license obtained for GFH375 under this agreement. This license will grant Verastem development and commercialization rights outside of Greater China, while GENFLEET retains rights within China.