Ongoing Trial Shows Positive Response Rates With MEK Inhibitor Combo in Ovarian Cancer Subset

Analysis of current data from the RAMP 201 study demonstrated positive response rates with avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer.

In particular, of 29 patients treated with avutometinib and defactinib, the objective response rate was 28%, meaning that these patients had a partial or complete response to treatment, according to a press release from Verastem, the manufacturer of avutometinib. In addition, this rate was 27% in patients with KRAS mutant disease and 29% in KRAS wild-type disease.

“The interim data from the ongoing phase 2 RAMP 201 trial show that the combination of avutometinib with defactinib yields encouraging response rates with a well-tolerated safety profile in women with heavily pretreated recurrent low-grade serous ovarian cancer,” said Dr. Susana Banerjee, lead investigator of the study, consultant medical oncologist at The Royal Marsden NHS Foundation Trust in England and team leader in women’s cancers at The Institute of Cancer Research in London, said in the release. “The contribution of defactinib, rates of tumor shrinkage in both KRAS mutant and KRAS wild-type (low-grade serous ovarian cancer) and a high disease control rate seen so far are important initial findings leading to the decision to move forward with the combination regimen.”

Most patients in the trial demonstrated tumor regression and had the overall disease control rate (defined as stable disease plus partial response to therapy) was 93%, according to the release. Of note, 62% of patients with evaluable data were still taking the combination treatment at a minimum follow-up of five months.

For patients treated with avutometinib alone, the overall response rate was 7% in the 30 patients with evaluable data with an overall disease control rate of 90%

For both treatment groups, researchers did not observe any new side effects, according to the release. The most common side effects related to treatment with avutometinib and defactinib included nausea, diarrhea, blurry vision, increase in blood creatine phosphokinase (indicating stress or injury to the heart, muscle tissue or brain), rash, leg swelling and fatigue. Nine percent of patients discontinued treatment from side effects.

“(Low-grade serous ovarian cancer) is a difficult disease to treat and one in urgent need of more effective and tolerable therapies,” said Dr. Rachel N. Grisham, section head of ovarian cancer and director of Westchester Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in New York, in the release. “The majority of patients with (low-grade serous ovarian cancer) present with advanced stage disease and experience chronic symptoms from their cancer.”

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