Dr Grisham on the Efficacy of Avutometinib Plus Defactinib in Gynecologic Mesonephric Cancer

“What we showed is that, in the first 13 patients [with stage I disease] accrued to the study, there were 2 confirmed and an additional 2 unconfirmed partial responses exceeding the predefined threshold.”

Rachel N. Grisham, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center; section head of Ovarian Cancer; and director of Gynecologic Medical Oncology, at Memorial Sloan Kettering Cancer Center Westchester, discusses interim results from a phase 2 study (NCT05787561), which evaluated avutometinib (VS-6766) plus defactinib (VS-6063) in patients with advanced or recurrent gynecologic mesonephric cancer.

For stage I, investigators accrued 13 patients with measurable, advanced or recurrent gynecologic mesonephric cancer. Patients were at least 18 years of age with measurable disease by RECIST 1.1 who had persistent or recurrent disease. They could not have received systemic anticancer therapy within 4 weeks of the study intervention, nor could they have received endocrine therapy within 1 week of study intervention. Those who underwent surgery within 4 weeks of the first dose of study treatment were excluded.

Grisham noted that it was remarkable how quickly they were able to enroll patients in the single-institution study, evaluating this approach in such a rare tumor. Participants received 3.2 mg of avutometinib twice weekly plus 200 mg of defactinib twice daily; this was given for the first 21 days of each 28-day cycle as part of a 3-weeks-on/1-week-off schedule. The primary end point was confirmed response rate by RECIST 1.1.

Data presented at the 2025 SGO Annual Meeting indicated that all patients experienced reduction in tumor lesions. Specifically, Grisham reported that there were 2 confirmed and an additional 2 unconfirmed partial responses, which exceeded the predefined threshold of 1 response that was needed to move to stage 2 of the study.

She added that the study has now completed its original planned accrual, and that in light of these data, protocol has been amended to allow for an expansion phase, where an additional 20 patients are being accrued. If the combination continues to show encouraging response rates, it may receive FDA approval for this population down the line, Grisham concluded.