Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2024

ENGOT-EN20/GOG-3083/XPORT-EC-042 A PHASE 3, randomized, placebo-controlled, double-blind, multicenter trial of Selinexor in maintenance therapy for patients with p53 wild-type, advanced or recurrent endometrial carcinoma (#568)

Kate Webber 1 2 , Ignace Vergote 3 4 , Mansoor R Mirza 5 , Robert Coleman 6 , Jose AP Fidalgo 7 , Bradley J Monk 8 , Giorgio Valabrega 9 , Brian Slomovitz 10 , Toon Van Gorp 3 4 , Kathleen Moore 11 , Jalid Sehouli 12 , David Cibula 13 , Tally Levy 14 , Gerassimos Aravantinos 15 , Kai Li 16 , Pratheek Kalyanapu 16 , Vicky Makker 17
  1. School of Clinical Sciences, Monash University, Clayton, Vic, Australia
  2. Monash Health, Clayton, VIC, Australia
  3. Leuven Cancer Institute, University Hospitals Leuven, Leuven
  4. Belgium and Luxembourg Gynaecological Oncology Group (BGOG), , Belgium
  5. Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
  6. GOG-Foundation and Sarah Cannon Research Institute (SCRI), Nashville, TN, USA
  7. GEICO and Hospital Clinico Universitario de Valencia. INCLIVA, CIBERONC, Spain
  8. GOG-Foundation and HonorHealth, University of Arizona, Creighton University, Phoenix, AZ, USA
  9. MITO and Department of Oncology, University of Torino, at Mauriziano Hospital, Turin, Italy
  10. Mount Sinai Medical Center, Florida International University, Miami Beach, FL, USA
  11. University of Oklahoma, Oklahoma City, OK, USA
  12. NOGGO and Department of Gynecology, European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, Charité–Berlin University of Medicine, Berlin, Germany
  13. CEEGOG and First Faculty of Medicine, Charles University and General University Hospital , Prague, Czech Republic
  14. ISGO and Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, affiliated with the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
  15. HeCOG and Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece
  16. Karyopharm Therapeutics, Newton, MA, USA
  17. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA

Introduction: Selinexor is a selective inhibitor of nuclear export via inhibition of exportin-1 (XPO1). In the ENGOT-EN5/GOG-3055/SIENDO study (NCT03555422), analysis of a pre-specified exploratory subgroup of patients with TP53 wild-type (wt) endometrial cancer (EC) was performed.  As of 01/04/2024, the mPFS for TP53wt patients who received selinexor compared with placebo was 28.4 vs 5.2 months (36.8-month follow-up, HR 0.44;95%CI 0.27-0.73). Benefit in mPFS was seen with selinexor vs placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36;95%CI 0.19–0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49;95%CI 0.18–1.34). Of the EC molecular subtypes, TP53wt tumors represent 50% of advanced and recurrent tumors.

Methods: XPORT-EC-042 (NCT05611931): a phase 3 randomized, double-blind, placebo-controlled study to evaluate efficacy and safety of selinexor maintenance in patients with TP53wt primary stage IV or recurrent EC, who achieved a PR or CR per RECISTv1.1 after completing ≥12 weeks of platinum-combination chemotherapy±immunotherapy. Among other inclusion/exclusion criteria, patients must be ≥18 years, have histologically confirmed EC, and TP53wt tumor (NGS confirmed). Patients are randomized 1:1 to oral selinexor 60mg or placebo once-weekly in 28-day cycles until progression, toxicity, or 3-years if in CR. A total of 220 patients will be enrolled globally. Primary endpoint is PFS based on RECISTv1.1 (Investigator-assessed). Key secondary endpoint is OS. Select secondary endpoints include safety assessments and PFS assessed by a blinded independent central review.

Current Trial Status: Patient enrollment is ongoing internationally, including at the following ANZGOG sites (as of 27th June 2024). NSW: Border Medical Oncology, Gosford Hospital and Wyong Hospital, Chris O’Brien Lifehouse, Newcastle Private Hospital QLD: ICON Cancer Centre Southport, Toowoomba Hospital SA: Royal Adelaide Hospital TAS: Royal Hobart Hospital VIC: Cabrini Malvern and Cabrini Brighton, Frankston Hospital, Monash Health, Peter MacCallum Cancer Centre.