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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Monday, October 6, 2025
The combination of avutometinib and defactinib could become a potential standard of care for treating patients with recurrent low-grade serous ovarian cancer, according to the study authors of a phase II trial published in the Journal of Clinical Oncology. The phase II study demonstrated the promising efficacy for the regimen as well as a manageable safety profile, especially for patients with KRAS mutations.
Avutometinib is an oral RAF/MEK clamp that blocks reactivation of MEK, and when combined with the selective FAK inhibitor defactinib, it leads to significant inhibition of tumor growth compared with avutometinib alone. The open-label phase II trial investigated the use of oral avutometinib as monotherapy or in combination with oral defactinib, in a randomized fashion, for patients with recurrent low-grade serous ovarian cancer after at least one line of platinum chemotherapy. The researchers elected to continue with the combination regimen for the expansion portion of the trial.
A total of 115 patients received the combination regimen of avutometinib at 3.2 mg twice per week plus defactinib at 200 mg twice per day. These patients had received a median of three prior lines of therapy.
The confirmed objective response rate, the primary endpoint, in the total combination regimen population was 31% (95% confidence interval [CI] = 23%–41%) and the median duration of response was 31.1 months (95% CI = 14.8–31.1). The median progression-free survival was 12.9 months (95% CI = 10.9–20.2).
For patients with KRAS mutations, the objective response rate was 44% vs 17% in patients with KRAS wild-type tumors. The median progression-free survival was 22.0 months in patients with KRAS mutations and 12.8 months without.
Most treatment-related nonlaboratory adverse events were grade 1 or 2 in severity. The most frequent events of grade 3 or above were elevated creatine phosphokinase in 24% of patients, diarrhea in 8%, and anemia in 5%. Ten percent of patients discontinued treatment due to adverse events.
Study authors, led by Susana N. Banerjee, PhD, MBBS, MA, FRCP, of The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, GTG-UK, London, United Kingdom, said that the findings “represent a promising advance in the management of patients with recurrent low-grade serous ovarian cancer, who currently have few effective treatment options.”
Going forward, the phase III RAMP 301 trial is further exploring use of the combination for women with recurrent low-grade serous ovarian cancer in comparison with investigator’s choice of therapy.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
