Verastem (VSTM) Study Update summary

High unmet need and patient impact

• LGSOC affects younger women, with 80% experiencing recurrence and limited effective, tolerable therapies available.

• Current standard of care yields low response rates (6-13%) and high discontinuation due to toxicity.

• No FDA-approved treatments exist for recurrent LGSOC, highlighting a significant unmet need.

Mechanism and rationale for avutometinib + defactinib

• 70% of LGSOC tumors are driven by RAS/MAPK pathway mutations; 30% are KRAS mutant.

• Avutometinib (RAF/MEK clamp) and defactinib (FAK inhibitor) target multiple resistance mechanisms and aim for deeper, more durable responses.

Study design and patient population

• RAMP 201 is a multicenter, randomized, open-label phase II trial evaluating avutometinib alone and in combination with defactinib in recurrent LGSOC, enrolling over 200 women, making it one of the largest LGSOC studies in a decade.

• Patients were heavily pretreated, with a median of three prior therapies, including chemotherapy, hormonal therapy, bevacizumab, and MEK inhibitors.

• Randomization was stratified by KRAS mutation status to ensure balanced representation of KRAS mutant and wild-type patients.

• The combination regimen of avutometinib (3.2 mg) and defactinib (200 mg) was selected as the go-forward dose based on efficacy and tolerability.

• The study included both KRAS mutant and wild-type patients, reflecting real-world diversity in LGSOC.