BOSTON — Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company developing new treatments for cancers driven by the RAS/MAPK pathway, announced encouraging preliminary results from the first two dose levels in its ongoing Phase 1/2a clinical trial of VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor. The study is evaluating VS-7375 as a monotherapy and in combination with cetuximab in patients with previously treated advanced KRAS G12D mutant solid tumors.
The first two monotherapy doses of 400 mg and 600 mg once daily cleared without any dose-limiting toxicities. Early findings show promising anti-tumor activity across multiple tumor types, including advanced pancreatic ductal adenocarcinoma. Notably, no nausea, vomiting, or diarrhea above Grade 1 severity was observed.
“Preliminary safety and tolerability data from our ongoing Phase 1/2a trial indicate that VS-7375 can be administered at efficacious doses while effectively managing gastrointestinal side effects,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “While still early, we are pleased to see anti-tumor activity among pre-treated patients with advanced pancreatic cancer and other solid tumors. As we continue monotherapy dose escalation, we are excited to open the combination cohort evaluating VS-7375 with cetuximab just months after trial initiation. By starting this combination cohort at a dose that has already shown monotherapy efficacy, we expect to accelerate our development program with additional standard-of-care combinations.”
The ongoing Phase 1/2a VS-7375-101 study is being conducted in the United States, with plans to expand internationally. The trial is assessing VS-7375’s safety, tolerability, and efficacy in patients with advanced KRAS G12D mutant solid tumors, including pancreatic ductal adenocarcinoma, as both monotherapy and combination therapy.
Of the five patients evaluated for efficacy so far, four experienced measurable tumor reduction and remain on treatment. The remaining patients have not yet reached their first assessment. The study is now testing a higher 900 mg daily monotherapy dose while also enrolling patients in a combination cohort with cetuximab, including those with advanced colorectal cancer.
“We’re encouraged by the early safety experience in this study, including the gastrointestinal tolerability and absence of cutaneous toxicities, along with early signs of anti-tumor activity,” said John Hayslip, M.D., chief medical officer of Verastem Oncology. “These preliminary findings are promising, and we look forward to the continued evaluation of VS-7375 both as monotherapy and in combination with cetuximab, as there remains a significant unmet need for therapies targeting KRAS G12D-mutant cancers.”
Pending Phase 1 results from the combination cohort, Verastem plans to initiate a colorectal cancer expansion arm. Following completion of monotherapy dose escalation to 900 mg daily, the company expects to determine the recommended Phase 2 dose and begin expanded efficacy and safety evaluations in advanced pancreatic and non-small cell lung cancers. Verastem anticipates reporting an interim safety and efficacy update from the ongoing trial in the first half of 2026.
