FDA Approves Avutometinib Plus Defactinib for KRAS-Mutated Recurrent Low-Grade Serous Ovarian Cancer
On May 8th, 2025, the United States Food and Drug Administration (FDA) granted accelerated approval to avutometinib plus defactinib for previously treated patients with KRAS-mutated recurrent low-grade serous ovarian cancer. This regulatory decision was based on results from the RAMP-201 trial.
In this multicenter, open-label study, 57 patients who received at least 1 prior line of systemic therapy including a platinum-based regimen, received 3.2 mg of avutometinib twice weekly (on days 1 and 4) plus 200 mg of defactinib twice daily taken for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity. The primary end point was overall response rate (ORR), assessed via blinded independent review. Key secondary end points included duration of response and safety.
At analysis, confirmed ORR was 44%. The duration of response range was 3.3 months to 31.1 months. The most common adverse reactions including laboratory abnormalities, occurring in ≥ 25% of patients, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, 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, urinary tract infection, and decreased neutrophil count.
The recommended dosage is 3.2 mg of oral avutometinib taken twice weekly on days 1 and 4 (in 4 0.8 mg capsules) plus 200 mg of oral defactinib taken twice daily for the first 3 weeks of each 4-week cycle until disease progression or unacceptable toxicity.
Source:
FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. Accessed on May 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-combination-avutometinib-and-defactinib-kras-mutated-recurrent-low
