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

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.

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Journal
Gynecologic Oncology
Published
2026-09-16
DOI
https://doi.org/10.1016/j.ygyno.2026.09.003
Primary Topic
Ovarian cancer diagnosis and treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Stephanie Lustgarten, Charlie Gourley, Premal H. Thaker, Andrew R. Clamp et al.
Gynecologic Oncology
Ovarian cancer diagnosis and treatment
article

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

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

Abstract

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.

Gynecologic OncologyVol. 213
Cleveland Clinic (US), Royal Marsden NHS Foundation Trust (GB), Memorial Sloan Kettering Cancer Center (US), Washington University in St. Louis (US), Cornell University (US), Brown University (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), Edinburgh Cancer Research (GB), Moffitt Cancer Center (US), Yale University (US), Florida Hospital Cancer Institute (US), VIB-KU Leuven Center for Cancer Biology (BE), Hospital Universitario Puerta de Hierro Majadahonda (ES), Centre Léon Bérard (FR), Florida Cancer Specialists & Research Institute (US), University Hospitals Seidman Cancer Center (US), The Christie NHS Foundation Trust (GB), Institut de Recherche en Cancérologie de Montpellier (FR), Nebraska Cancer Specialists (US), Verastem (United States) (US), Minnesota Oncology (US), University of Virginia (US), The Ohio State University (US), University of Nebraska Medical Center (US), European Institute of Oncology (IT), KU Leuven (BE)
Verastem Oncology
Peace, Justice and strong institutions
Openalex Percentile: Top 9%
Ovarian cancer diagnosis and treatment
DOIOpen Access PDFOpenAlex
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