Verastem (VSTM) Study Update summary

Study Design and Patient Population

• RAMP 201 is a large, randomized, open-label phase II trial evaluating avutometinib plus defactinib in recurrent low-grade serous ovarian cancer (LGSOC), enrolling over 200 women, many heavily pretreated with up to nine prior therapies.

• The study included both KRAS mutant and wild-type patients, with stratification to ensure balanced representation.

• Key inclusion criteria were recurrent LGSOC, prior chemotherapy, measurable disease, and prior MEKi allowed.

• The combination regimen was selected for further study based on superior efficacy and tolerability compared to monotherapy or lower-dose regimens.

• Avutometinib is a RAF/MEK clamp and defactinib is a FAK inhibitor, both targeting RAS/MAPK-driven cancers.

Efficacy and Safety Results

• The overall response rate (ORR) was 31%, with 44% in KRAS mutant and 17% in KRAS wild-type patients; 82% experienced tumor shrinkage.

• Median progression-free survival (PFS) was 12.9 months overall, 22 months in KRAS mutant, and 12.8 months in KRAS wild-type patients.

• Median duration of response was 31.1 months overall and in KRAS mutant, and 9.2 months in KRAS wild-type.

• The discontinuation rate due to adverse events was 10%, with no new safety signals and manageable side effects.

• Dose interruptions and reductions were frequent but allowed for prolonged therapy.

Regulatory and Commercial Updates

• NDA submission for recurrent KRAS mutant LGSOC is on track for October 2024, seeking Accelerated Approval and Priority Review, with anticipated launch in 2025.

• The regulatory package includes data from both RAMP 201 and the supportive FRAME study.

• RAMP 301 phase III confirmatory trial is ongoing, enrolling both KRAS mutant and wild-type patients, and may support broader indications.

• Plans are in place to submit the full RAMP 201 dataset to NCCN for guideline consideration, critical for reimbursement.

• The FDA granted Breakthrough Therapy and Orphan Drug Designations to the combination for LGSOC.