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The phase 3 ENGOT-EN20/GOG-3083/XPORT-EC-042 trial (NCT05611931) is evaluating selinexor (Xpovio) in maintenance therapy after systemic therapy for patients with p53 wild-type (p53wt), advanced or recurrent endometrial carcinoma.1
"The purpose of the ENGOT-EN-20/GOG-3083/XPORT-EC-042 study is to evaluate the efficacy and safety of selinexor compared with placebo as a maintenance treatment in patients with advanced/recurrent TP53 wild-type endometrial cancer following response to prior systemic therapy," said Brian M. Slomovitz, MD, director of Gynecologic Oncology, and co-chair of the Cancer Research Committee at Mount Sinai Medical Center, and professor of obstetrics and gynecology at Florida International University.
About the Phase 3 XPORT-EC-042 Study
Trial Name: A Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial of Selinexor in Maintenance Therapy After Systemic Therapy for Patients With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma
ClinicalTrials.gov Identifier: NCT05611931
Sponsor: Karyopharm Therapeutics Inc.
Recruitment Contact: Karyopharm Medical Information, (888) 209-9326, firstname.lastname@example.org
Completion Date: August 31, 2025
"The incorporation of molecular classification of endometrial cancer has been integral in targeting the best therapy for the right patient at the right time. We look forward to the rapid enrollment of the ENGOT-EN20/GOG-3083/XPORT-EC-042 study to evaluate the benefit of selinexor as a targeted maintenance therapy personalized for women with TP53 wt endometrial cancer," Slomovitz added.
The study aims to evaluate the efficacy and safety of selinexor when used as a maintenance treatment in patients with p53wt endometrial cancer who have achieved a partial response (PR) or complete response (CR) after completing at least 12 weeks of platinum-based therapy.
In the randomized, placebo-controlled, double-blind, multicenter, phase 3 study, a total of 220 patients aged 18 years and older with histologically confirmed endometrial cancer including, endometrioid, serous, undifferentiated, and carcinosarcoma, deemed TP53wt by next generation sequencing (NGS) will be enrolled. Patients are required to have completed a single line, at least 12 weeks of platinum-based therapy, and achieved confirmed partial response (PR) or CR.1,2
Other requirements for enrollment include having an ECOG performance status of 0-1, adequate bone marrow function and organ function within 2 weeks before starting study drug, a life expectancy of at least 12 weeks. Patients also must be fit to receive investigational therapy.
Patients will be stratified by primary stage IV vs recurrent, and PR vs CR. Once enrolled, patients will be randomized in a 1:1 ratio to receive maintenance therapy with either selinexor or placebo. Selinexor will be given at a fixed dose of 60 mg orally, once weekly, on days 1, 8, 15, and 22 of each 28-day cycle. Patients in the placebo comparator arm will be given matching placebo for selinexor oral tablets once a week on days 1, 8, 15, and 22 of each 28-day cycle.
The primary end point being evaluated in the study is progression-free survival (PFS) assessed by Investigator as per RECIST v1.1. Secondary end points include overall survival, number of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, severity of TEAEs, time to first subsequent therapy, time to second subsequent therapy, number of patients with significant changes in clinical laboratory values, vital signs, and physical examination reported as an AE, PFS, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol-5 Dimensions-5 Levels.
Exploratory end points of the study include PFS per histology subtypes and per other molecular features, CR rate, duration of CR, tumor biomarkers, and pharmacokinetics.2
“XPORT-EC-042 follow this idea of looking at these p53 wild-type groups, because we think these are the ones who have the most benefit. Investigators are going to look at the partial response or complete response in patients, place them on this maintenance therapy group, and see exactly the benefit that we're experiencing with this maintenance. I think this is going to be a positive study, but we won't know until it’s completed. And it's really going to help in the landscape of the maintenance therapy for this group of patients, where up to now we don't have a great standard of care for them, John P. Diaz, MD, director of Robotic Surgery, Baptist Health; lead physician for clinical trials in gynecologic oncology, at Miami Cancer Institute, as well as the director of the Center of Excellence in Minimally Invasive Gynecologic Surgery at Baptist Health, and director of Ambulatory Surgery Center at Baptist Health Cancer Care told Targeted Oncology.
The study is ongoing and actively recruiting patients in Arizona, California, Florida, Illinois, Indiana, Louisiana, Michigan, Mississippi, Missouri, Nevada, New York, Oklahoma, Pennsylvania, South Dakota, Tennessee, Texas, Wisconsin, Israel, and Spain, with an estimated study completion date of August 31, 2025.1
"Treatment options for patients with advanced/recurrent endometrial cancer are rapidly evolving. While immune checkpoint inhibitors showed significant benefit in patients with MSI-H/dMMR tumors, there is a high unmet need in those with MSS/pMMR tumors for which there is limited evidence of benefit," added Slomovitz.
Selinexor in maintenance therapy after systemic therapy for participants with p53 wild-type, advanced or recurrent endometrial carcinoma (XPORT-EC-042). ClinicalTrials.gov. Updated July 12, 2023. Accessed July 26, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05611931
SlomovitzB, Fidalgo AP, Hamilton E, et al. Long-term follow up of selinexor maintenance in patients with TP53wt advanced or recurrent endometrial cancer: A pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study. Presented at: 2023 July ASCO Plenary Series. Abstract 427956.