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Gynecologic oncology · 2026

Long-term efficacy and safety of avutometinib + defactinib in recurrent low-grade serous ovarian cancer: Results of a 2-year follow-up of ENGOT-OV60/GOG-3052/RAMP 201.

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Grisham Rachel N, Van Nieuwenhuysen Els, Santin Alessandro D, D'Hondt Véronique, Thaker Premal H, Clamp Andrew R, Moore Kathleen N, Aghajanian Carol, Oaknin Ana, O'Malley David M, Monk Bradley J, Colombo Nicoletta, Prendergast Emily N, Ring Kari L, Ray-Coquard Isabelle, Rose Peter G, Gourley Charlie, Holloway Robert W, Chon Hye Sook, Van Gorp Toon, Youssoufian Hagop, Salinas Erin, Lustgarten Stephanie, Banerjee Susana N

Аннотация

OBJECTIVE: In a phase 2 study, avutometinib (RAF/MEK clamp) and defactinib (FAK inhibitor) demonstrated efficacy in patients with recurrent low-grade serous ovarian cancer (LGSOC). Here, we report updated safety and efficacy data with 2 years of follow-up.

METHODS: Patients with recurrent LGSOC after ≥1 line of platinum chemotherapy were enrolled. Data from the combination of avutometinib 3.2 mg twice weekly plus defactinib 200 mg twice daily were summarized. Endpoints included duration of response (DOR) and progression-free survival (PFS).

RESULTS: A total of 115 patients received avutometinib + defactinib (58 KRAS mt, 57 KRAS wt). Median follow-up of ongoing patients was 24.9 months. Median (95% CI) DOR was 31.1 months (14.8 to not evaluable [NE]); 31.1 months (21.2 to NE) in patients with a KRAS mutation and 12.0 months (5.5 to NE) in patients without a KRAS mutation. Median (95% CI) PFS was 12.9 months (10.9 to 19.6); 19.6 months (11.1 to 36.6) in patients with a KRAS mutation and 12.7 months (7.4 to 12.9) in patients without a KRAS mutation. The most common grade ≥ 3 treatment-related adverse events were increased creatine phosphokinase (26%), diarrhea (8%), and anemia (7%). A total of 12% of patients discontinued treatment due to an adverse event and no treatment-related deaths occurred.

CONCLUSIONS: With a median follow-up of approximately 2 years (about twice the duration of the primary analysis), the combination of avutometinib and defactinib demonstrated durable efficacy in patients with recurrent LGSOC and no new safety signals.