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Plenary 01: Oral Abstract Presentations
AS11. Ovarian cancer
PO004LBA/#1515  Efficacy and safety of avutometinib + defactinib in recurrent low-grade serous ovarian cancer following prior systemic therapy
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  1. Rachel Grisham1,
  2. Carol Aghajanian1,
  3. Els Van Nieuwenhuysen2,
  4. Manuel Rodrigues3,
  5. Kari Ring4,
  6. Alessandro Santin5,
  7. Nicoletta Colombo6,
  8. Emily Prendergast7,
  9. Premal Thaker8,
  10. Kathleen Moore9,
  11. Erin Salinas10,
  12. Isabelle Ray-Coquard11,
  13. Hye Sook Chon12,
  14. Peter Rose13,
  15. Ana Oaknin14,
  16. Andrew Clamp15,
  17. Mitul Gandhi16,
  18. Bradley Monk17,
  19. Robert Holloway18,
  20. Toon Van Gorp19,
  21. Michel Fabbro20,
  22. Christine Gennigens21,
  23. Nicholas Wojtynek22,
  24. Stephanie Lustgarten23 and
  25. Susana Banerjee24
  1. 1Memorial Sloan Kettering Cancer Center,, Gynecologic Medical Oncology Service, New York, USA
  2. 2Leuven Cancer Institute, Gynaecology and Obstetrics, Leuven, Belgium
  3. 3Institut Curie, Department of Medical Oncology, Inserm U830, Paris, France
  4. 4University of Virginia, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Charlottesville, USA
  5. 5Yale School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Gynecologic Oncology, New Haven, USA
  6. 6European Institute of Oncology, Gynecologic Oncology, Monza, Italy
  7. 7Minnesota Oncology, Gynecologic Oncology, Minneapolis, USA
  8. 8Washington University in St. Louis School of Medicine, Division of Gynecologic Oncology, St. Louis, USA
  9. 9Stephenson Cancer Center, Gynecologic Oncology, oklahoma city, USA
  10. 10Compass Oncology, Gynecologic Oncology, Portland, USA
  11. 11CENTRE LEON BERARD, Oncology, LYON, France
  12. 12H.Lee Moffitt Cancer Center and Research Institute, Department of Gynecologic Oncology, Tampa, USA
  13. 13Cleveland Clinic Foundation, Women’s Health Institute, Cleveland, USA
  14. 14Vall d’Hebron University Hospitl, Oncology, Baracelona, Spain
  15. 15The Christie NHS Foundation Trust and University of Manchester, Medical Oncology, Manchester, UK
  16. 16Virginia Cancer Specialists, Virginia Cancer Specialists, Gainesville, USA
  17. 17Director, Principal Investigator,, Community Research Development, Honorhealth Research Institute, Scottsdale, USA
  18. 18Advent Health Cancer Institute, Gynecologic Oncology Program, Orlando, USA
  19. 19University Hospitals Leuven, Leuven Cancer Institute, Oncology, Leuven, Belgium
  20. 20ICM Val d’Aurelle Parc Euromedecine, Oncologie Médicale, Montpellier, Gineco, Paris, France
  21. 21CHU Liège, Liège, Liège, Belgium
  22. 22Verastem Oncology, Medical Affairs, Needham, MA, USA
  23. 23Verastem, Inc., Biostatistics, Needham, USA
  24. 24National Cancer Research Institute (NCRI), The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK

Abstract

Introduction Avutometinib is a novel small molecule RAF/MEK clamp. FAK activation is a resistance mechanism to RAF/MEK inhibition; defactinib, a small molecule FAK inhibitor, has shown synergistic antitumor activity with avutometinib. Avutometinib + defactinib demonstrated a 45% ORR and a mild to moderate, manageable/reversible safety profile in heavily pretreated (mLoT=4) recurrent LGSOC (KRAS mt + wt) (ENGOT-ov60/GOG-3052/RAMP 201, NCT04625270).

Methods This post-hoc analysis of the phase 2 ENGOT-ov60/GOG-3052/RAMP 201 study in recurrent LGSOC (06Apr2023 data cutoff) was performed to assess efficacy (Part A; confirmed ORR via blinded independent central review) and safety (all treated patients) in the context of 1) lines of prior systemic therapy (1–3 LoT, ≥4 LoT) and 2) best response to most recent prior treatment in the metastatic/recurrent setting (PR/CR, no PR/CR; as assessed by treating investigator).

Results In the combination arm, similar ORRs were observed in patients that were treated with 1–3 (5/11, 45.5%) and ≥4 LoT (8/18, 44.4%) (table 1). Prior to enrollment in RAMP 201, only 2/23 (8.7%) patients responded to their last prior treatment, whereas the combination of avutometinib + defactinib yielded an ORR of 43.5% (10/23) in this subgroup (table 2). The safety profiles of avutometinib + defactinib were similar in the less and more heavily pretreated subgroups, and both analyses were consistent with previously reported safety data. The majority of TRAEs were mild to moderate, manageable/reversible.

View this table:
Abstract PO004LBA/#1515 Table 1

ORR by number of prior therapies per blinded independent central review

View this table:
Abstract PO004LBA/#1515 Table 2

ORR by best response to most recent prior treatment in the metastatic/recurrent setting per blinded independent central review

Conclusion/Implications Avutometinib + defactinib demonstrated robust efficacy (ORR) in recurrent LGSOC irrespective of the number of prior therapies, and for most of which, response to previous therapy was poor.

https://doi.org/10.1136/ijgc-2023-IGCS.4

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