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
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.
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BibTeX
@article{grisham2026longterm,
title = {{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}},
author = {Rachel Grisham and Els van Nieuwenhuysen and Alessandro Santin and Véronique d'Hondt and Premal Thaker and Andrew Clamp and Kathleen Moore and Carol Aghajanian and Ana Oaknin and David O'Malley and Bradley Monk and Nicoletta Colombo and Emily Prendergast and Kari Ring and Isabelle Ray-Coquard and Peter Rose and Charlie Gourley and Robert Holloway and Hye Sook Chon and Toon van Gorp and Hagop Youssoufian and Erin Salinas and Stephanie Lustgarten and Susana Banerjee},
journal = {Gynecologic Oncology},
year = {2026},
month = oct,
doi = {10.1016/j.ygyno.2026.09.003},
url = {https://hal.science/hal-05801007v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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
AU - Rachel Grisham
AU - Els van Nieuwenhuysen
AU - Alessandro Santin
AU - Véronique d'Hondt
AU - Premal Thaker
AU - Andrew Clamp
AU - Kathleen Moore
AU - Carol Aghajanian
AU - Ana Oaknin
AU - David O'Malley
AU - Bradley Monk
AU - Nicoletta Colombo
AU - Emily Prendergast
AU - Kari Ring
AU - Isabelle Ray-Coquard
AU - Peter Rose
AU - Charlie Gourley
AU - Robert Holloway
AU - Hye Sook Chon
AU - Toon van Gorp
AU - Hagop Youssoufian
AU - Erin Salinas
AU - Stephanie Lustgarten
AU - Susana Banerjee
PY - 2026
DA - 2026/10/15
JO - Gynecologic Oncology
DO - 10.1016/j.ygyno.2026.09.003
UR - https://hal.science/hal-05801007v1
AB - 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.
SN - 0090-8258
SN - 1095-6859
ER -