FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer
Regulatory approval: On May 8, 2025, the FDA granted accelerated approval to the co-pack of avutometinib plus defactinib (Avmapki Fakzynja Co-pack; Verastem, Inc.) for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer who have received prior systemic therapy. Approval was supported by RAMP-201 (NCT04625270), where confirmed ORR was 44% (95% CI 31–58) by blinded independent review; duration of response ranged from 3.3 to 31.1 months.
FDA accelerated approval: avutometinib + defactinib in KRAS-mutated recurrent LGSOC
Type: Regulatory approval (accelerated)
Date: 2025-05-08
Agency: US FDA
The FDA granted accelerated approval to the combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack; Verastem, Inc.) for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.
Supporting evidence
Efficacy was evaluated in RAMP-201 (NCT04625270), an open-label, multicenter trial enrolling 57 adults with measurable KRAS-mutated recurrent LGSOC. Patients had received ≥1 prior systemic therapy, including a platinum-based regimen. KRAS status was determined by prospective local tumor tissue testing.
Primary endpoint: ORR by blinded independent review (RECIST v1.1).
- Confirmed ORR: 44% (95% CI 31–58)
- DOR range: 3.3 to 31.1 months
Safety and dosing
Common adverse reactions (≥25%; including lab abnormalities) included increased CPK, nausea, fatigue, increased AST/ALT, rash, diarrhea, musculoskeletal pain, edema, and vitreoretinal disorders/visual impairment, among others.
Recommended dosing: avutometinib 3.2 mg orally twice weekly (Day 1, Day 4) plus defactinib 200 mg orally twice daily, both for the first 3 weeks of each 4-week cycle until progression or unacceptable toxicity.
The review used RTOR and priority review; the regimen received breakthrough therapy and orphan drug designations.