FDA

Avutometinib and defactinib granted accelerated approval for rare ovarian cancer

May 12, 2025

Brand name: Avmapki Fakzynja Co-pack

Generic name: avutometinib and defactinib

Manufacturer: Verastem

Approval date: May 8, 2025

FDA granted accelerated approval to the combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack) for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.

Efficacy

Efficacy was evaluated in the open-label, multicenter RAMP-201 trial (NCT04625270) that included 57 adult patients with measurable KRAS-mutated recurrent LGSOC. Patients were required to have received at least one prior systemic therapy, including a platinum-based regimen. KRAS mutation status was determined by prospective local testing of tumor tissue. Patients received avutometinib 3.2 mg PO twice weekly (Day 1 and Day 4) and defactinib 200 mg PO bid, both taken for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity.

The major efficacy outcome measure was overall response rate (ORR), and an additional efficacy outcome measure was duration of response (DOR). Confirmed ORR was 44% (95% confidence interval [CI], 31-58) and the DOR range was 3.3 months to 31.1 months.

Safety

The most common adverse reactions (≥25%), including lab abnormalities, were increased CPK, nausea, fatigue, increased AST, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased ALT, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, UTI, and decreased neutrophil count.

Recommended dose

The recommended avutometinib dosage is 3.2 mg (four 0.8 mg capsules) PO twice weekly (Day 1 and Day 4) for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity. The recommended defactinib dose is 200 mg (one tablet) PO bid for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity.

Sources:

FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low

FDA Approves the Avmapki™ Fakzynja™ combination therapy as the first-ever treatment for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer. [News release]. 2025. https://investor.verastem.com/news-releases/news-release-details/fda-approves-avmapkitm-fakzynjatm-combination-therapy-first-ever

Avmapki Fakzynja Co-Pack (avutometinib and defactinib). [package insert]. Verastem. https://www.verastem.com/pdf/avmapki-fakzynja-co-pack-full-prescribing-information.pdf Revised May 2025. Accessed May 9, 2025.