The combination of avutometinib and defactinib in treating recurrent low-grade serous ovarian cancer: a plain language summary of the Phase II clinical trial ENGOT-OV60/GOG-3052/RAMP 201

Abstract

Avutometinib; Defactinib; Plain language summary

Avutometinib; Defactinib; Resumen en lenguaje sencillo

Avutometinib; Defactinib; Resum en llenguatge senzill

What is this summary about?This plain language summary describes the results of the ENGOT-OV60/ GOG-3052/RAMP 201 clinical study, which were published in 2025. The Phase II study evaluated treatments for patients with a rare type of ovarian cancer, low-grade serous ovarian cancer (LGSOC). The study specifically involved those whose cancer came back or persisted, despite already having surgery and previous chemotherapy. Researchers investigated the effect of avutometinib on its own and in combination with defactinib to see which treatment would be more effective and to determine if both treatments were safe. They also investigated the combination of a lower dose of avutometinib with defactinib. All trial participants were tested for a specific KRAS genetic mutation (non-hereditary, also called somatic). The main goal of the study was to determine the confirmed objective response rate of each treatment. This is the percentage of patients whose cancer shrinks by at least 30% after treatment and maintains this shrinkage for at least 2 months. The study also closely monitored for any adverse events associated with each treatment and looked at other measures of treatment effectiveness.What were the results?The percentage of patients with an objective response was 31% in the combination treatment group and 17% in the avutometinib-only group. Amongst patients receiving the combination, the objective response rate was 44% in the group of participants with a KRAS mutation and 17% in the group without a KRAS mutation. The lower dose of avutometinib used in combination with defactinib was not as effective as the standard dose.In the standard dose combination treatment group, most adverse events were not severe (categorized as grade 1 or 2 on a scale of 0 to 5) and were managed with dose holds or dose reductions. The most frequent adverse events reported were nausea, increased creatine phosphokinase (CPK), diarrhea, peripheral edema, and rash. A total of 10% of participants discontinued treatment due to adverse events.What do the results mean?The results of the study support using the combination of avutometinib and defactinib as a treatment option for women with recurrent LGSOC.Clinical trial number: NCT06072781.