GenFleet Therapeutics announced that its partner Verastem Oncology dosed the first patient in their TARGET-D 201 phase II registration-directed trial evaluating GFH375 (known as VS-7375 outside of China), an investigational oral KRAS G12D (ON/OFF) inhibitor, to treat patients with KRAS G12D-mutated metastatic pancreatic ductal carcinoma (PDAC). TARGET-D 201 is an open-label, multi-center study in the U.S. to evaluate both the monotherapy and in combination with full-dose cetuximab in patients with second-line metastatic PDAC. The study also evaluates the combination with cetuximab in the first-line PDAC setting. FDA’s fast track designations were previously granted for VS-7375 for the treatment of KRAS G12D-mutated advanced or metastatic pancreatic cancer in all lines of setting, and for treatment of KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC).
Verastem initiated the TARGET-D 101 study in patients with advanced KRAS G12D-mutated solid tumors in 2025, and the enrollment is ongoing with monotherapy dose escalation progressing from 400 mg through 900 mg QD without dose-limiting toxicities (DLT). The study also evaluates the efficacy and safety in combination with cetuximab or chemotherapy: anti-tumor activity was observed at multiple dose levels from 400 to 900 mg QD both as monotherapy and in combination with cetuximab across multiple KRAS G12D-driven tumors. DLT assessment has been cleared for VS-7375 at 900 mg QD combined with full-dose cetuximab in colorectal cancer (CRC) and for VS-7375 at 600 mg QD plus chemotherapy (AG) in PDAC.
According to preliminary study data issued by Verastem, as of June 12, 2026, monotherapy demonstrated a favorable and manageable safety profile at the 600 mg QD (n=57) and 900 mg QD (n=25) dose levels in the TARGET-D 101 study. The rates of Grade 3 treatment-related adverse events (TRAEs) remained low. TRAEs were primarily low-grade nausea, vomiting and diarrhea, and the vast majority of the gastrointestinal (GI) side effects were effectively managed with standard supportive care measures. A very low frequency of rash was observed, and no rash was above Grade 1. No clinically meaningful cytopenias or liver function abnormalities were reported. Emerging longer-term follow-up data are encouraging, with no clinically significant cumulative toxicities observed to date.
Additionally, Verastem is expected to report an update on the TARGET-D 101 trial in H2 2026. It plans to report first patient dosing for the TARGET-D 202 and TARGET-D 203 trials in mid-2026 and also intends to communicate with the U.S. FDA before year-end to align on phase III pivotal trial designs for first-line metastatic PDAC, CRC and NSCLC. First patient enrollment across all three pivotal phase III trials is projected in the first half of 2027. Besides, Verastem and Erasca announced their intent to enter into an agreement agreement to evaluate the VS-7375+ Erasca’s Pan RAS (ERAS-0015) combinational regimen in KRAS G12D mutant preclinical models, and in a combinational trial for patients with advanced solid tumors, subject to the execution of a definitive agreement and the outcome of the preclinical evaluation.
About GFH375/VS-7375
GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays.
GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China.
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