New Targeted Therapy Combination Approved for a Rare Ovarian Cancer
The FDA has approved avutometinib and defactinib for certain patients with KRAS-mutated low-grade serous ovarian cancer.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to avutometinib and defactinib (Avmapki Fakzynja Co-pack) for the treatment of adult patients with low-grade serous ovarian cancer that harbors mutant KRAS and has recurred after prior systemic therapy.
Avutometinib and defactinib are targeted therapies that block signaling pathways associated with malignant growth to help blunt the cancer-promoting impact of abnormal KRAS activity. This is the first FDA approval for avutometinib and defactinib, and the first specifically for KRAS-mutated ovarian cancer.
The accelerated approval is based on results from the open-label phase II RAMP-201 trial, in which 57 adult patients with recurrent, KRAS-mutated low-grade serous ovarian cancer who had received prior systemic therapy were treated with avutometinib and defactinib. Overall, 44% of patients experienced tumor responses, which lasted from 3.3 to 31.1 months.
The recommended dose for avutometinib is 3.2 mg orally twice weekly, and the recommended dose for defactinib is 200 mg orally twice daily. Both treatments are administered in concurrent four-week cycles: three weeks treatment, followed by one week without treatment, until disease progression or unacceptable toxicity.
Low-grade serous ovarian cancer is a rare form of ovarian cancer that often recurs or progresses after initial treatment. According to federal statistics, it was estimated that 20,890 individuals would be diagnosed with ovarian cancer and approximately 12,730 patients would die of the disease in the United States in 2025.
The FDA rendered its decision on May 8, 2025. Accelerated approval means that continued approval may be contingent upon a confirmatory trial. Please check this FDA web page for information about any accelerated approvals in oncology that may have been subsequently withdrawn and are no longer FDA-approved. Check this resource for updated information on all therapeutics regulated by the FDA.