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  • #523 Initial efficacy and safety results from ENGOT-Ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC)

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Oral Sessions
06. Ovarian cancer
#523 Initial efficacy and safety results from ENGOT-Ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC)
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  1. Susana N Banerjee1,
  2. Kari L Ring2,
  3. Els Van Niewenhuysen3,
  4. Michel Fabbro4,
  5. Carol Aghajanian5,
  6. Ana Oaknin6,
  7. Nicoletta Colombo7,
  8. Alessandro D Santin8,
  9. Andrew R Clamp9,
  10. Kathleen N Moore10,
  11. Peter G Rose10,
  12. O’Malley David M11,
  13. Hye Sook Chon12,
  14. Erin A Salinas13,
  15. Emily N Prendergast14,
  16. Stephanie Lustgarten15,
  17. Manuel Rodrigues16,
  18. Christine Gennigens17,
  19. Bradley J Monk18 and
  20. Rachel N Grisham5
  1. 1The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, National Cancer Research Institute (NCRI), London, UK
  2. 2Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, USA
  3. 3University Hospitals Leuven, Leuven, Belgium
  4. 4ICM Val d’Aurelle Parc Euromedecine, Oncologie médicale, Montpellier, GINECO, Paris, France
  5. 5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, USA
  6. 6Gynaecologic Cancer Programme;Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  7. 7Department of Medicine and Surgery, University of Milan-Bicocca, Italy and Gynecologic Oncology Program, European Institute of Oncology IRCCS, Milan, Italy
  8. 8Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Gynecologic Oncology, Yale School of Medicine, New Haven, USA
  9. 9Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester, UK
  10. 10Stephenson Oklahoma Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, USA
  11. 11The Ohio State University, James Comprehensive Cancer Center, Columbus, USA
  12. 12Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, USA
  13. 13Compass Oncology, Portland, USA
  14. 14Gynecologic Oncology, Minnesota Oncology and Metro-Minnesota Community Oncology Research Consortium, Minneapolis, USA
  15. 15Verastem Inc., Needham, USA
  16. 16Department of Medical Oncology, INSERM U830, Institut Curie, Paris, France
  17. 17Department of Medical Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium
  18. 18HonorHealth, University of Arizona, Creighton University, Phoenix, USA

Abstract

Introduction/Background LGSOC, a RAS/MAPK driven cancer, constitutes ≤10% of ovarian cancer, with no FDA-approved treatments. Avutometinib is a novel small molecule RAF/MEK clamp. Focal adhesion kinase (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 high confirmed and durable response rate (objective response rate [ORR]=46%) in recurrent LGSOC.

Methodology A phase 2, multicenter, randomized study evaluated avutometinib ± defactinib in patients with KRAS mutant (mt) and KRAS wild-type (wt) recurrent LGSOC to identify an optimal regimen based on confirmed ORR by blinded independent central review (Part A) and determine efficacy (Part B) (NCT04625270). Patients were randomized to avutometinib (mono) or avutometinib + defactinib (combo). Key inclusion criteria: histologically-confirmed recurrent LGSOC, known KRAS status, prior platinum chemotherapy. Unlimited prior therapies, including MEK inhibitor, were permitted. Efficacy results from Part A (evaluable patients, N=64) and safety data from all patients (N=151) are presented (April 2023 data cutoff).

Results In Part A, median number of prior regimens was 3 for mono, 4 for combo. A 45% confirmed ORR was observed for combo (60% KRAS mt, 29% KRAS wt) and 10% for mono (13% KRAS mt, 6% KRAS wt). Three of 4 patients previously treated with MEK inhibitor showed confirmed partial response on combo arm. Median time to response: 7.3 months (mono) and 5.5 months (combo). Most treatment-related adverse events (AEs) for combo (n=81) were grade 1–2, with a low proportion of dose reductions (17%) and discontinuations due to AEs (12.3%) in the combo arm.

Conclusion Interim data support avutometinib + defactinib as an active go-forward regimen in heavily-pretreated recurrent LGSOC, regardless of KRAS status. No new safety signals were observed; most AEs were mild to moderate.

https://doi.org/10.1136/ijgc-2023-ESGO.29

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