Sistema de Salut de Catalunya
Institut Català de la Salut
[Banerjee SN] The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, GTG-UK, London, United Kingdom. [Van Nieuwenhuysen E] University Hospitals Leuven, Leuven Cancer Institute, BGOG, Leuven, Belgium. [Aghajanian C] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, Weill Cornell Medical College, New York, NY. [D’Hondt V] Institut du Cancer de Montpellier (ICM) Val d’Aurelle Parc Euromedecine, Oncologie Médicale, GINECO, Montpellier, France. [Monk BJ] Florida Cancer Specialists, West Palm Beach, FL. [Clamp A] Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, GTG-UK, Manchester, United Kingdom. [Oaknin A] Medical Oncology Service, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-09-16T10:31:22Z
2025-09-16T10:31:22Z
2025-09-01
Efficacy; Safety; Serous ovarian cancer
Eficacia; Seguridad; Cáncer de ovario seroso
Eficàcia; Seguretat; Càncer d'ovari serós
Purpose: This study evaluated the efficacy and safety of avutometinib (rapidly accelerated fibrosarcoma/mitogen-activated extracellular signal-regulated kinase [MEK] clamp) alone or in combination with defactinib (focal adhesion kinase inhibitor) in patients with recurrent low-grade serous ovarian cancer (LGSOC). Methods: In this phase II, open-label study, patients with recurrent, measurable LGSOC after ≥1 line of platinum chemotherapy were stratified by tumor Kirsten rat sarcoma virus homolog (KRAS) mutation status and randomly assigned to oral avutometinib 4.0 mg two times per week monotherapy or avutometinib 3.2 mg two times per week in combination with oral defactinib 200 mg two times per day. The combination was selected as the go-forward regimen for expansion. The primary end point was objective response rate (ORR) by blinded independent central review. Results: A total of 115 patients received the go-forward combination regimen. Patients had a median of 3 (range, 1-9) prior lines of therapy, including hormonal (86%), bevacizumab (51%), and MEK inhibitor (22%). Confirmed ORR was 31% (95% CI, 23% to 41%) with a median duration of response of 31.1 months (95% CI, 14.8 to 31.1). ORR was 44% in KRAS-mutant and 17% in KRAS wild-type cohorts. The median progression-free survival was 12.9 months (95% CI, 10.9 to 20.2) overall and 22.0 months (95% CI, 11.1 to 36.6) and 12.8 months (95% CI, 7.4 to 18.4) in KRAS-mutant and wild-type cohorts, respectively. The most frequent grade ≥3 treatment-related adverse events (AEs) were elevated creatine phosphokinase (24%), diarrhea (8%), and anemia (5%). Ten percent of patients discontinued because of AEs. Conclusion: The efficacy and safety profile of avutometinib in combination with defactinib support this combination as a potential standard of care for recurrent LGSOC. A randomized phase 3 study of avutometinib and defactinib versus investigator's choice of therapy for women with recurrent LGSOC is currently enrolling (RAMP301; ClinicalTrials.gov identifier: NCT06072781). Trial registration: ClinicalTrials.gov NCT04625270 NCT06072781 NCT04625270.
Supported by Verastem Oncology (Needham, MA) and conducted in collaboration with GOG Foundation and ENGOT.
Article
Published version
English
Avaluació de resultats (Assistència sanitària); Ovaris - Càncer - Tractament; Quimioteràpia combinada; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cystadenocarcinoma::Cystadenocarcinoma, Serous; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::cistoadenocarcinoma::cistoadenocarcinoma seroso; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
American Society of Clinical Oncology
Journal of Clinical Oncology;43(25)
https://doi.org/10.1200/JCO-25-00112
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
