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LB007/#1548  Efficacy and safety of avutometinib ± defactinib in recurrent low grade serous ovarian cancer: primary analysis of ENGOT-OV60/GOG-3052/RAMP 201
  1. Susana Banerjee1,
  2. Carol Aghajanian2,
  3. Els Van Nieuwenhuysen3,
  4. Alessandro Santin4,
  5. Kari Ring5,
  6. Nicoletta Colombo6,7,
  7. Premal Thaker8,
  8. Emily Prendergast9,
  9. Kathleen Moore10,
  10. Hye Sook Chon11,
  11. Andrew Clamp12,
  12. David O’malley13,
  13. Bradley Monk14,
  14. Alfonso Cortés-Salgado15,
  15. Michel Fabbro16,
  16. Elsa Kalbacher17,
  17. Toon Van Gorp3,
  18. Stephanie Lustgarten18,
  19. Hagop Youssoufian18 and
  20. Rachel Grisham2
  1. 1The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, GTG-UK, London, UK
  2. 2Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
  3. 3University Hospitals Leuven, Leuven Cance Institute, BGOG, Leuven, Belgium
  4. 4Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Gynecologic Oncology, Yale School of Medicine, New Haven, CT, United States of America
  5. 5Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, VA, United States of America
  6. 6Gynecologic Oncology Program, European Institute of Oncology, IRCCS, Milan, Italy
  7. 7Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
  8. 8Division of Gynecologic Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States of America
  9. 9Gynecologic Oncology, Minnesota Oncology, Minneapolis, MN, United States of America
  10. 10Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
  11. 11Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, United States of America
  12. 12Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, GTG-UK, Manchester, UK
  13. 13The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, United States of America
  14. 14Florida Cancer Specialists, West Palm Beach, FL, United States of America
  15. 15Medical Oncology Department, Hospital Ramón y Cajal, Ramón y Cajal Health Research Institute (IRYCIS), Ramón y Cajal University Hospital, GEICO, Madrid, Spain
  16. 16ICM Val d’Aurelle Parc Euromedecine, Oncologie Médicale, Montpellier, GINECO, Paris, France
  17. 17Medical Oncology Department, CHU J Minjoz, GINECO, Besançon, France
  18. 18Verastem Oncology, Needham, MA, United States of America

Abstract

Introduction Low grade serous ovarian cancer (LGSOC) is a rare, clinically distinct cancer commonly driven by RAS/MAPK pathway alterations. Avutometinib ([A] oral RAF/MEK clamp) + defactinib ([D] oral FAK inhibitor) is being investigated in recurrent LGSOC. We report the primary analysis of A±D from RAMP 201.

Methods Patients with recurrent, measurable LGSOC after at least one line of platinum chemotherapy were enrolled. Patients were randomized to A (4.0mg BIW) monotherapy or A (3.2mg BIW) + D (200mg BID). A+D was selected for expansion. Subsequently a 1.6mg dose of A +D was evaluated. The primary endpoint is ORR per RECISTv1.1 by BICR.

Results At the 30June2024 visit cutoff, 115 patients were enrolled to A (3.2mg BIW) + D (200mg BID). Median age was 54 (range, 21-87) and patients had a median of 3 (range, 1-9) prior lines of therapy. Prior therapies included endocrine (86%), bevacizumab (51%), and MEK inhibitor (22%). Confirmed ORR of 31% was observed (44% KRAS mt; 17% KRAS wt); median DOR, 31.1mo and median PFS, 12.9mo. The most common non-laboratory treatment-related AEs (all grades, grade ≥3) were nausea (67.0%, 2.6%) and diarrhea (58.3%, 7.8%). The most common laboratory abnormality was increased blood creatinine phosphokinase (60.0%, 24.3%). Discontinuations due to AEs were infrequent (10%). Results from all cohorts will be presented.

Conclusion/Implications A+D was well tolerated allowing prolonged exposure to therapy. ORR and durable responses observed are clinically meaningful in this heavily pretreated population and support the potential of A+D as a new standard of care for recurrent LGSOC.

Abstract LB007/#1548 Table 1

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