May 9, 2025 -- A new oral cancer drug combination has gained a quick federal nod after clinical trials found that it provides significant and longer-lasting relief for a rare ovarian cancer that doesn’t respond well to standard therapies. This marks the first and only FDA-approved medicine for low-grade serous ovarian cancer (LGSOC) that tests positive for a gene change known as the KRAS mutation.
The treatment includes two drugs known as avutometinib and defactinib and is marketed as Avmapki Fakzynja Co-Pack. It is for adult patients who have already tried other therapies, offering hope to about 6,000 to 8,000 women in the United States who are living with this disease.
LGSOC is a rare, slow-growing cancer affecting about 80,000 people worldwide, mostly women
in their 20s-30s or 50s-60s. About 30% of cases involve changes in the KRAS gene, which fuel cancer growth. It’s difficult to treat, often doesn’t respond well to standard therapies, and tends to come back. While people may live for around 10 years with LGSOC, it can significantly impact
physical and mental health, fertility, and quality of life.
The FDA’s decision was based on a clinical trial involving 57 patients with recurrent KRAS-positive LGSOC, all of whom had received at least one prior treatment. Patients were given oral doses of avutometinib twice weekly and defactinib twice daily for the first three weeks of each four-week cycle, continuing until cancer progression or severe side effects occurred. Results showed that the tumor shrank in 44% of patients, with the response lasting from 3.3 months to 31.1 months.
The drug combo works by blocking proteins that promote cancer growth and resistance to treatment. Avutometinib blocks a protein called MEK, but when that protein is blocked, another protein called FAK can become more active. That’s where the second medicine, defactinib, comes in, blocking the FAK protein to prevent the cancer from fighting back. For each four-week cycle, patients take Avmapki twice a week and Fakzynja twice a day for three weeks, as long as the treatment’s working and the side effects are tolerable.
The most common side effects include nausea, vomiting, diarrhea, abdominal pain, indigestion, constipation, mouth sores, itching, tiredness, skin rash, dry or itchy skin, muscle or joint pain, swelling, changes in blood test results (such as elevated liver enzyme and bilirubin levels, low hemoglobin levels and blood cell counts), eye problems, shortness of breath, cough, and urinary tract infections. According to the company’s safety information, doctors must advise their patients about using effective contraception during the therapy as the new treatment can harm a fetus. Patients will also be monitored for liver function, skin toxicity, muscle disease (rhabdomyolysis), and vision problems during their treatment.
The company added that the accelerated approval was based on how well the treatment works, and full approval may depend on results from a confirmatory trial.
