Verastem Begins Submission for Ovarian Cancer Combination

Verastem Oncology has begun a rolling submission of a new drug application (NDA) to the FDA for the combination of avutometinib and defactinib to treat adults with low-grade serous ovarian cancer (LGSOC). The company is seeking accelerated approval in patients who have recurrent KRAS-mutant disease.

Serous ovarian cancer is the largest group of ovarian cancers in the epithelial lining, which covers the outside of the ovary. Low grade serous ovarian cancer is rare subtype and is less sensitive to chemotherapy than high grade serous ovarian cancer. Patients with ovarian cancer who have KRAS mutations have been found to have poor outcomes. Between 6,000 and 8,000 women in the United States and 80,000 worldwide are living with this disease. Currently, there are no FDA-approved treatments specifically for recurrent LGSOC.

Avutometinib is a RAF/MEK clamp that may overcome resistance and block tumor growth. Defactinib is a selective FAK inhibitor that has demonstrated synergy with avutometinib.

The initial sections of the application will include the nonclinical and quality sections. Verastem plans to submit in the second half of 2024 a primary efficacy analysis based on the RAMP 201 study with 12 months of follow up.

RAMP 201 is a phase 2 study evaluating avutometinib and defactinib combination in patients with recurrent LGSOC with 115 patients; enrollment is complete. As of February 2024, interim data continued to show robust overall response rates (ORR) and durable responses with low discontinuation rates due to adverse events in patients with a minimum follow-up of five months. In patients with five months of follow up, the overall response rate was 27%. Additionally, 14 patients had stable disease or unconfirmed partial response, company officials said during an investor presentation.

Dan Paterson

“In the second half of this year, we anticipate completing our NDA submission with the mature data from the RAMP 201 trial and discussing with the FDA a path forward for patients with KRAS wild-type disease. We also expect to present the mature dataset at a medical meeting in the second half of 2024,” Dan Paterson, president and CEO of Verastem, said in a news release.

Verastem is currently enrolling patients and activating sites for RAMP 301, an international confirmatory phase 3 trial. Previously, the FDA granted Breakthrough Therapy Designation (BTD) for the combination for treatment of patients with recurrent LGSOC.