Accelerated approval is granted by the USFDA to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer

On May 8, 2025, the Food and Drug Administration approved the use of avutometinib and defactinib (Avmapki Fakzynja Co-pack, Verastem, Inc.) for adults with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have already received treatment before.

The effectiveness was evaluated in RAMP-201 (NCT04625270), a study that included 57 adult patients with measurable KRAS-mutated recurrent low-grade serous ovarian cancer. Patients were mandated to have undergone a minimum of one previous systemic therapy, which included a platinum-based regimen. The KRAS mutation status was established using prospective local analysis of tumor samples. Patients were administered avutometinib 3.2 mg orally biweekly (on Day 1 and Day 4) and defactinib 200 mg orally twice daily, for the initial 3 weeks of each 4-week cycle, unless disease progression or intolerable toxicity occurred.

The primary effectiveness endpoint was the overall response rate (ORR), evaluated by a blinded independent review committee in accordance with RECIST v1.1. An extra efficacy outcome measure was the duration of response (DOR). The confirmed overall response rate (ORR) was 44% (95% confidence interval: 31, 58), and the duration of response (DOR) ranged from 3.3 months to 31.1 months.

The most prevalent adverse reactions (≥25%), including laboratory abnormalities, comprised elevated creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, reduced hemoglobin, elevated alanine aminotransferase, vomiting, increased blood bilirubin, elevated triglycerides, diminished lymphocyte count, abdominal pain, dyspepsia, acneiform dermatitis, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, xerosis, dyspnea, cough, urinary tract infection, and diminished neutrophil count.

The recommended dose of avutometinib is 3.2 mg, which is taken as four 0.8 mg capsules by mouth every two weeks (on Day 1 and Day 4) for the first 3 weeks of each 4-week cycle, and this continues until the disease gets worse or side effects become too severe. The recommended dose of defactinib is 200 mg (one tablet) taken by mouth two times a day for the first 3 weeks of each 4-week cycle, and this continues until the disease gets worse or side effects become too severe.