First two monotherapy dose levels (400 mg QD and 600 mg QD) cleared, with no dose-limiting toxicities reported

Promising anti-tumor activity observed in patients with various solid tumors, including advanced pancreatic ductal adenocarcinoma

No nausea, vomiting, or diarrhea greater than Grade 1 was observed

Enrollment initiated for VS-7375 in combination with cetuximab in patients with advanced KRAS G12D mutant solid tumors, including colorectal cancer

Plan to report an interim safety and efficacy update on the Phase 1/2a trial in the first half of 2026

Verastem Oncology (NASDAQ:VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK-pathway-driven cancers, today announced encouraging preliminary data from the first two dose levels in its ongoing Phase 1/2a clinical trial evaluating VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in patients with previously-treated advanced KRAS G12D mutant solid tumors. In addition, while monotherapy dose escalation continues, the Company announced it has initiated patient enrollment for the first dose escalation combination cohort evaluating VS-7375 with cetuximab.

"Preliminary safety and tolerability data from our ongoing Phase 1/2a trial indicate that VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, 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 of VS-7375 that has previously demonstrated monotherapy efficacy, we expect to accelerate our clinical development program with other standard-of-care combination cohorts."

VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans underway to expand globally, and is evaluating the safety and efficacy of VS-7375 in patients with previously-treated advanced KRAS G12D mutant solid tumors, including advanced pancreatic ductal adenocarcinoma (PDAC), both as monotherapy and in combination with other standard of care treatments.

In the study, VS-7375 cleared both the 400 mg daily (QD) and 600 mg QD monotherapy doses with no dose-limiting toxicities (DLTs) observed. In addition, no new safety signals have been observed relative to earlier data presentations in both PDAC and non-small cell lung cancer (NSCLC) by our partner, GenFleet Therapeutics, in its ongoing Phase 1 /2 clinical study in China evaluating VS-7375 (known as GFH375). Specifically, at the two dose levels evaluated in the U.S. cohorts, no nausea, vomiting, or diarrhea greater than Grade 1 were reported. Monotherapy dose escalation in the VS-7375-101 study started at the efficacious doses identified in GenFleet's study, 400 mg QD and 600 mg QD. GenFleet chose 600 mg QD as their recommended Phase 2 dose (RP2D) in China.

Of the five efficacy evaluable patients in the VS-7375-101 study with at least one scan, four out of five patients have had a tumor reduction and are still on treatment. The remaining patients receiving either the 400 mg QD or 600 mg QD doses have not yet reached their first response assessment. The study's dose escalation continues with evaluating 900 mg QD monotherapy and the combination cohort evaluating VS-7375 with cetuximab is now open and enrolling patients. The cohort will enroll patients with advanced solid tumors, including colorectal cancer.

"We're encouraged by the early safety experience in this study, including the GI tolerability we've seen to date and absence of cutaneous toxicities, along with the early signs of anti-tumor activity. These preliminary findings are promising, and we look forward to the continued evaluation of VS-7375 both as monotherapy and now in combination with cetuximab as there remains a significant unmet need for treatments specifically targeting KRAS G12D-mutant cancers," said John Hayslip, M.D., chief medical officer of Verastem Oncology.

Subject to the results of the Phase 1 dose escalation combination of VS-7375 and cetuximab, Verastem plans to initiate a combination expansion cohort in colorectal cancer. Following the ongoing monotherapy dose escalation to 900 mg QD, the Company expects to select the recommended Phase 2 dose and advance subsequent efficacy and safety analysis of monotherapy VS-7375 in patient expansion cohorts with advanced PDAC and NSCLC. The Company plans to report an interim safety and efficacy update on the Phase 1/2a trial of VS-7375 in the first half of 2026.