FDA Grants Fast Track Designation to VS-7375 for KRAS G12D–Mutated Advanced Pancreatic Cancer

FDA

The FDA has granted fast track designation to VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, for the treatment of adult patients with KRAS G12D–mutated locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), including patients on first-line treatment and patients who have received at least 1 prior line of systemic therapy.1

VS-7375, also known as GFH375, is under evaluation in China in patients with KRAS G12D–mutated advanced solid tumors in an ongoing phase 1/2 dose-escalation trial (NCT06500676). Updated preliminary safety and efficacy results presented at the 2025 ASCO Annual Meeting showed that no dose-limiting toxicities (DLTs) were observed across evaluated dose levels. Treatment-related adverse effects (TRAEs) of grade 3 or 4 severity occurred in 29% of all evaluable patients, irrespective of tumor type (n = 62), and no grade 5 TRAEs were reported. The most common any-grade TRAEs included diarrhea (69%), nausea (68%), and vomiting (61%). TRAEs led to dose reductions, treatment interruptions, and treatment discontinuation in 5%, 11%, and 3% of patients, respectively.

Among efficacy-evaluable patients with PDAC (n = 23), the objective response rate (ORR) was 52% (90% CI, 34%-70%), and the disease control rate (DCR) was 100% (90% CI, 88%-100%).

“The fast track designation for VS-7375 underscores the importance of our potential best-in-class KRAS G12D (ON/OFF) inhibitor. As we continue enrollment in our US phase 1/2a clinical trial [NCT07020221], our goal is to accelerate the program’s development, given the lack of FDA-approved, KRAS G12D–targeted treatments for people with KRAS G12D[–mutated] cancers,” Dan Paterson, president and CEO of Verastem Oncology, stated in a news release.1

Phase 1/2 Study Breakdown

The ongoing first-in-human phase 1/2 trial being conducted in China is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of VS-7375 in patients with advanced solid tumors harboring KRAS G12D mutations.2 Eligible participants have locally advanced or metastatic solid tumors, have experienced disease progression following prior standard systemic therapies, and had an ECOG performance status of 0 or 1.

In the phase 1 portion of the study, VS-7375 is being evaluated at once-daily doses of 100 mg, 200 mg, 400 mg, 600 mg, 750 mg, and 900 mg, along with a twice-daily dose of 300 mg. The recommended phase 2 dose will then be evaluated in tumor-specific cohorts during phase 2, including dedicated groups for patients with KRAS G12D–mutated PDAC, non–small cell lung cancer, colorectal cancer, and other solid tumors. Treatment is being given until disease progression or unacceptable toxicity.

The primary objectives of phase 1 are safety and tolerability of the agent; secondary objectives include antitumor activity, pharmacokinetics, and biomarkers. ORR, DCR, duration of response, progression-free survival, and overall survival are efficacy end points in phase 2, with additional end points for safety and biomarkers.

“Given the encouraging initial safety and efficacy results in China reported by our partner, GenFleet Therapeutics, at ASCO this year, we are excited to be advancing VS-7375 in the US to evaluate it in advanced pancreatic cancer and non–small cell lung cancer and in combination with cetuximab in advanced solid tumors, including colorectal cancer,” Paterson explained.

References

1. Verastem Oncology granted fast track designation for VS-7375 for the treatment of KRAS G12D-mutated locally advanced or metastatic pancreatic cancer. News release. Verastem Oncology. July 24, 2025. Accessed July 24, 2025. https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-granted-fast-track-designation-vs-7375
2. Ai X, Zhou A, Wu L, et al. A first-in-human phase I/II study of GFH375, a highly selective and potent oral KRAS G12D inhibitor in patients with KRAS G12D mutant advanced solid tumors. J Clin Oncol. 2025;43(suppl 16):3013. doi:10.1200/jco.2025.43.16_suppl.3013