Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma

NCT05611931RecruitingPHASE3INTERVENTIONAL

Summary

The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v 1.1\]) after completing at least 12 weeks of platinum-based therapy. A total of 276 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.

Key Facts

Lead Sponsor

Karyopharm Therapeutics Inc

Enrollment

276

Start Date

2023-04-18

Completion Date

2026-08-01

Study Type

INTERVENTIONAL

Official Title

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

Interventions

SelinexorMatching Placebo for selinexor

Conditions

Endometrial Cancer

Eligibility

Age Range

18 Years+

Sex

ALL

Inclusion Criteria: Patients must meet all of the following inclusion criteria in order to be eligible to participate in this study:

* Adults (Aged ≥ 18 years)
* Histologically confirmed endometrial cancer (endometrioid, serous, undifferentiated, or carcinosarcoma sub-types) that is TP53 wild type by central NGSHistologically confirmed EC including endometrioid, serous, undifferentiated, and carcinosarcoma
* Must have completed at least 12 weeks of platinum-based chemotherapy (with or without immune checkpoint inhibitors), with a confirmed partial or complete response according to RECIST v1.1
* Must be able to initiate C1D1 within 3-8 weeks after last platinum dose
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow function and organ function

Exclusion Criteria: Patients meeting any of the following exclusion criteria are not eligible to participate in this study:

* Uterine sarcomas, clear cell or small cell carcinoma with neuroendocrine differentiation
* Palliative radiotherapy administered within 14 days of intended C1D1
* Any gastrointestinal dysfunction that could interfere with the absorption of oral study therapy
* Serious psychiatric or medical conditions that could interfere with study participation or would make study involvement unreasonably hazardous
* Previous treatment with an XPO1 inhibitor
* Stable disease or disease progression after platinum-based chemotherapy
* Pregnancy, breastfeeding, or other legal/ethical restrictions to trial participation
* Known dMMR/MSI-H EC tumors that are medically eligible to receive an immune checkpoint inhibitor

Outcome Measures

Primary Outcomes

Investigator assessed Progression Free Survival (PFS) per RECIST v1.1

Time frame: From randomization until disease progression (PD) or death, whichever occurs first (up to 34 months)

Secondary Outcomes

Overall Survival (OS)

Time from randomization to death due to any cause

Time frame: Up to 34 months

Safety and tolerability of study drug (selinexor and placebo)

The safety and tolerability of study drug (selinexor and placebo) will be evaluated based on adverse event (AE) reports, physical examination results (including vital signs), and clinical laboratory results, by means of the occurrence, nature, and severity of AEs via Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.

Time frame: From start of study drug administration up to 34 months

Time to First Subsequent Therapy (TFST)

Time from randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first

Time frame: From randomization until date of initiation of first therapy after discontinuation of study drug or death, whichever occurs first (up to 34 months)

Time to Second Subsequent Therapy (TSST)

Time from randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first

Time frame: From randomization until date of initiation of second therapy after discontinuation of study drug or death, whichever occurs first (up to 34 months)

Progression-free survival after initiating a next-line treatment (PFS2)

Time from randomization until the progression event after initiating a next-line treatment or death due to any cause, whichever occurs first

Time frame: From randomization until the next-line progression event or death due to any cause, up to 34 months

Progression-free Survival (PFS) as assessed by a Blinded Independent Central Review (BICR), per RECIST v1.1

Time frame: From randomization until disease progression (PD) or death, whichever occurs first (up to 34 months)

EuroQol-5 Dimensions-5 Levels Quality of Life Questionnaire (EQ-5D-5L)

EQ-5D-5L is a generic questionnaire that assesses health status as perceived by the patient across 5 categories (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and overall.

Time frame: From baseline and at specified timepoints up to 34 months

Locations

The University of Alabama at Birmingham, Birmingham, United States

Honor Health, Phoenix, United States

University of Arkansas for Medical Sciences, Little Rock, United States

UC DAVIS, Davis, United States

City of Hope National Medical Center, Duarte, United States

Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine, United States

City of Hope at Irvine Lennar, Irvine, United States

Cancer and Blood Specialty Clinic, Los Alamitos, United States

UCLA - Women's Health Clinical Research Unit, Los Angeles, United States

Long Beach Memorial Medical Center, Los Angeles, United States

UC Irvine, Orange, United States

Stanford University, Palo Alto, United States

California Pacific Medical Center, San Francisco, United States

Highlands Ranch Hospital, Highlands Ranch, United States

University of Colorado Cancer Center, Highlands Ranch, United States

Broward Health Medical Center, Fort Lauderdale, United States

Mount Sinai Comprehensive Cancer Center, Miami Beach, United States

Advent Health, Orlando, United States

Grady Hospital, Atlanta, United States

Emory University, Atlanta, United States

Georgia Cancer Center at Augusta University, Augusta, United States

Northeast Georgia Medical Center, Gainesville, United States

Illinois Cancer Specialists, Arlington Heights, United States

NorthShore University Health System, Evanston, United States

Northwest Cancer Center, Dyer, United States

Goshen Health, Goshen, United States

St Vincent Hospital, Indianapolis, United States

Memorial Hospital of South Bend, South Bend, United States

University of Iowa, Iowa City, United States

Our Lady of the Lake Hospital, Inc., Baton Rouge, United States

LSU Health Sciences Center New Orleans, New Orleans, United States

Trials365, LLC, Shreveport, United States

Tufts Medical Center, Boston, United States

Karmanos Cancer Institute, Detroit, United States

USON - Minnesota Oncology Hematology, Minneapolis, United States

University of Minnesota, Minneapolis, United States

St. Dominic's Gynecologic Oncology, Jackson, United States

Midwest Ventures Group HCA MId America Division, Kansas City, United States

Washington University School of Medicine, St Louis, United States

Intermountain Health St. Vincent Regional Hospital, Billings, United States

Women's Cancer Center of Nevada, Las Vegas, United States

Center Of Hope, Reno, United States

Hackensack Meridian Health Jersey Shore University Medical Center, Neptune City, United States

Women's Cancer Care Associates, LLC, Albany, United States

NYU Langone Hospital-Long Island, Mineola, United States

Northwell Health - Zuckerberg Cancer Center, New Hyde Park, United States

Mount Sinai Chelsea, New York, United States

Perlmutter Cancer Center at NYU Langone Health, New York, United States

Mount Sinai, New York, United States

Lenox Hill Hospital, New York, United States

Northwell Health - Queens Cancer Center, Rego Park, United States

University of Rochester, Rochester, United States

Atrium Health Levine Cancer Institute, Charlotte, United States

Duke Cancer Center, Durham, United States

University of Cincinnati Medical Center, Cincinnati, United States

MetroHealth, Cleveland, United States

Zangmeister Cancer Center, Columbus, United States

ProMedica Flower Hospital, Sylvania, United States

University of Oklahoma Health Sciences Center, Oklahoma City, United States

Oklahoma Cancer Specialists and Research Institute, LLC, Tulsa, United States

Oncology Associates of Oregon, Eugene, United States

Providence Portland Medical Center, Portland, United States

Alliance Cancer Specialists, Langhorne, United States

Magee - Women's Hospital, Pittsburgh, United States

Allegheny Health Network - West Penn Hospital, Pittsburgh, United States

Avera, Sioux Falls, United States

Chattanooga's Program in Women's Oncology, Chattanooga, United States

The West Clinic, PLLC dba West Cancer Center, Germantown, United States

University of Tennessee Medical Center, Knoxville, United States

University of Tennessee Health Science Center, Memphis, United States

USON - Texas Oncology, Austin Central, Austin, United States

Parkland Health & Hospital System, Dallas, United States

Texas Oncology - Dallas, Dallas, United States

University of Texas Southwestern Medical Center, Dallas, United States

Texas Oncology - Fort Worth, Fort Worth, United States

Houston Methodist, Houston, United States

Texas Oncology - San Antonio, San Antonio, United States

Texas Oncology - The Woodlands, The Woodlands, United States

Texas Oncology, PC, Tyler, Tyler, United States

University of Utah, Salt Lake City, United States

University of Virginia, Charlottesville, United States

Swedish Cancer Institute, Seattle, United States

University of Wisconsin Hospital and Clinics, Madison, United States

Medical College of Wisconsin/ Freodtert Hospital, Milwaukee, United States

Border Medical Oncology & Haematology, Albury, Australia

Macarthur Cancer Therapy Centre, Campbelltown, Australia

Chris O'Brien Lifehouse, Camperdown, Australia

Central Coast LHD - Gosford & Wyong Hospitals, Gosford, Australia

Newcastle Private Hospital, New Lambton Heights, Australia

Royal North Shore Hospital, Saint Leonards, Australia

Westmead Hospital, Wentworthville, Australia

ICON Cancer Centre Southport, Southport, Australia

Toowoomba Hospital, Toowoomba, Australia

Royal Hobart Hospital, Hobart, Australia

Box Hill Hospital - Eastern Health (Oncology), Box Hill, Australia

Monash Health, Clayton, Australia

Frankston Hospital, Frankston, Australia

Cabrini Health, Malvern, Australia

Peter MacCallum Cancer Centre/RWH/RMH, Melbourne, Australia

The Royal Adelaide Hospital, Southport, Australia

Cliniques Universitaires St. Luc, Brussels, Belgium

AZ Sint Lucas, Ghent, Belgium

UZ Leuven, Leuven, Belgium

CHU Ambroise Pare, Mons, Belgium

CHU UCL Namur, Site Sainte-Elisabeth, Namur, Belgium

Tom Baker Cancer Centre, Calgary, Canada

Cross Cancer Institute, Edmonton, Canada

Nova Scotia Health / QEII Health Sciences Centre / Atlantic Clinical Cancer Research Unit, Halifax, Canada

Princess Margaret, Toronto, Canada

Sunnybrook Research Institute, Toronto, Canada

Centre Hospitalier de l'Université de Montréal, Montreal, Canada

McGill University Health Centre (MUHC), Montreal, Canada

Hospital Maisonneuve-Rosemont, Montreal, Canada

University Hospital Brno, Brno, Czechia

University Hospital Ostrava, Ostrava, Czechia

UH Královské Vinohrady, Prague, Czechia

General University Hospital in Prague, Prague, Czechia

Hospital Na Bulovce, Prague, Czechia

High Technology Hospital Medcenter, Batumi, Georgia

Todua Clinic, Tbilisi, Georgia

LTD New Hospitals, Tbilisi, Georgia

Tbilisi Cancer Center, Tbilisi, Georgia

JSC - K.Eristavi National Center of Experimental and Clinical Surgery, Tbilisi, Georgia

Caucasus Medical Centre, Tbilisi, Georgia

LTD Innova Medical Center, Tbilisi, Georgia

Multiprofile Clinic "Consilium Medulla", Tbilisi, Georgia

Charite Berlin Universitatsmedizin, Berlin, Germany

Universitätsklinikum Hamburg Eppendorf, Hamburg, Germany

University Hospital Dresden, Kiel, Germany

Universitatsklinikum Schleswig-Holstein, Kiel, Germany

Helios Klinikum Krefeld, Krefeld, Germany

Universitätsklinik Leipzig, Leipzig, Germany

Universitätsfrauenklinik Mainz, Mainz, Germany

Universitätsmedizin Mannheim, Mannheim, Germany

Klinik und Poliklinik fur Frauenheilkunde und Geburtshilfe GroBhadern, Munich, Germany

Klinikum Südstadt Rostock, Rostock, Germany

Universitätsfrauenklinik Ulm, Ulm, Germany

IASO Hospital, Marousi, Greece

Alexandra Hospital, Athens, Greece

Hygeia Hospital, Athens, Greece

Euromedica General Clinic, Thessaloniki, Greece

Unit of Gynecol.Oncol., Dept.Obstet.Gynecol., Clinical Center, University of Debrecen, Debrecen, Hungary

Petz Aladár University Teaching Hospital, Győr, Hungary

St. Vincent's University Hospital, Dublin, Ireland

Cork University Hospital, Cork, Ireland

St. James Hospital, Dublin, Ireland

Galway University, Galway, Ireland

University Hospital Waterford, Waterford, Ireland

Hillel-Yaffe Medical Center, Hadera, Israel

Wolfson Medical Center, Holon, Israel

Hadassah Medical Center, Jerusalem, Israel

Sheba Medical Center, Ramat Gan, Israel

IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy

ASST Spedali Civili Di Brescia, Brescia, Italy

IRCCS Istituto Romagnolo Per Lo Studio Del Tumori "Dino Amadori" - IRST S.R.L., Meldola, Italy

San Raffaele Hospital, Milan, Italy

Istituto Nazionale dei Tumori IRCCS - MILANO S. C. Ginecologia Oncologica, Milan, Italy

Instituto Europeo di Oncologia, Milan, Italy

Humanitas San Pio X Hospital, Milan, Italy

Ospedale San Gerardo - Asst Monza, Monza, Italy

"Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" - NAPOLI Struttura Complessa Oncologia Medica Uro-Ginecologica", Naples, Italy

Istituto Oncologico Veneto, Padua, Italy

Universita di Pisa, Pisa, Italy

Nuovo Ospedale di Prato, Prato, Italy

Fondazione Policlinico Universitario Agostino Gemelli - ROMA, Roma, Italy

Ospedale Ostetrico Ginecologico Sant'Anna, Torino, Italy

AO Ordine Mauriziano, Torino, Italy

St. Elisabeth Cancer Institute, Bratislava, Slovakia

UH Bratislava, Bratislava, Slovakia

National Cancer Institute, Bratislava, Slovakia

UH Trenčín, Trenčín, Slovakia

Soon Chun Hyang University Hospital Cheonan, Cheonan, South Korea

Severance Hospital (Yonsei University Health System), Seoul, South Korea

Samsung Changwon Hospital, Changwon, South Korea

National Cancer Center (NCC), Goyang-si, South Korea

CHA University/Bundang CHA General Hospital, Seongnam-si, South Korea

Seoul National University Hospital, Seoul, South Korea

Gangnam Severance Hospital, Seoul, South Korea

Seoul National University Bundang Hospital, Seoul, South Korea

Korea University Anam Hospital, Seoul, South Korea

Samsung Medical Center, Seoul, South Korea

Asan Medical Center, Seoul, South Korea

Hospital Universitario Donostia, Donostia / San Sebastian, Spain

Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

ICO Badalona, Badalona, Spain

Hospital Universitari Vall d' Hebrón, Barcelona, Spain

Hospital Clinic de Barcelona, Barcelona, Spain

Institut Catala d'Oncologia Hospitalet, Barcelona, Spain

Hospital Universitario Reina Sofía, Córdoba, Spain

Institut Catala d'Oncologia de Girona, Girona, Spain

Hospital Universitario Virgen de las Nieves, Granada, Spain

MD Anderson Cancer Center Madrid, Madrid, Spain

Hospital Universitario Ramón y Cajal, Madrid, Spain

Hospital Universitario Clinico San Carlos, Madrid, Spain

H 12 de Octubre, Madrid, Spain

Hospital Universitario La Paz, Madrid, Spain

Hospital Universitatrio Virgen de la Victoria, Málaga, Spain

Virgen de la Arrixaca University Clinical Hospital, Murcia, Spain

Hospital Universitario Virgen del Rocío, Seville, Spain

Instituto Valenciano de Oncología, Valencia, Spain

Hospital Clínico Universitario de Valencia, Valencia, Spain

Hospital LaFe Uacenlia, Valencia, Spain

Hospital Miguel Servet, Zaragoza, Spain

Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan

TaiChung Veterans General Hospital, Taichung, Taiwan

Chi Mei Medical Center, Tainan, Taiwan

Mackay Memorial Hospital, Taipei, Taiwan

Taipei Veterans General Hospital, Taipei, Taiwan

Taipei Medical University- Shuang Ho Hospital, Ministry of Health and Welfare, Taipei, Taiwan

Chang Gung Memorial Hospital, Taoyuan, Taiwan

Ankara Baskent Hospital, Çankaya, Turkey (Türkiye)

Çukurova University, Adana, Turkey (Türkiye)

Adana Baskent Hospital, Adana, Turkey (Türkiye)

Hacettepe University Oncology Hospital, Ankara, Turkey (Türkiye)

Memorial Ankara Hospital, Ankara, Turkey (Türkiye)

Cerrahpasa University, Istanbul, Turkey (Türkiye)

Acibadem Atakent Hospital, Istanbul, Turkey (Türkiye)

Linked Papers

2025-09-18

Molecular Characterization and Clinical Implications of Endometrial Cancer

The classification of endometrial cancer (EC) has diverged from traditional histologic features based on microscopic appearance to objective molecular characterization. Molecular characterization of EC is pivotal to inform prognosis and to guide therapeutic recommendations. First described by the Cancer Genome Atlas, molecular profiling was later revised by the Proactive Molecular Risk Classifier for Endometrial Cancer and TransPORTEC algorithms to create clinically applicable and relatively easy-to-implement molecular classification systems. Since 2020, the World Health Organization recommended molecular classification of EC into four distinct prognostic subtypes: ECs with polymerase ε (POLE) pathogenic mutations assessed by gene sequencing, mismatch repair deficiency determined by immunohistochemistry or microsatellite instability assay, and p53 abnormalities determined by immunohistochemistry or next-generation sequencing. The final molecular subtype without any of these defining features is called “no specific molecular profile” (NSMP). This is further stratified by estrogen receptor (ER) immunohistochemistry status. Patients with cancers identified as POLE pathogenic mutations have the best prognosis with almost no recurrence or death events, followed by those with strong ER-positive NSMP cancers. Mismatch repair deficiency ECs have intermediate prognosis, whereas p53 abnormalities and ER-negative NSMP have the worst prognosis. Other molecular and pathologic biomarkers of interest include tumor mutational burden, human epidermal growth factor receptor 2, L1 cell adhesion molecule, β-catenin (CTNNB1), and lymph vascular space invasion, which may have prognostic and predictive implications. The current guidelines will continue to evolve; however, at minimum, it is recommended that all patients undergo testing for mismatch repair, p53, and ER, and POLE testing may be prioritized in select circumstances. Molecular classification provides the critical framework to deliver effective, personalized, high-quality care and informs clinical trial design. Molecular assessment ensures consistent diagnosis and provides prognostic information and predictive data to guide appropriate management.

2024-08-05

ENGOT-EN20/GOG-3083/XPORT-EC-042 – A phase III, 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: rationale, methods, and trial design

Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 ( To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent Eligible patients must have histologically confirmed endometrial cancer, The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. A total of 220 patients will be enrolled. Accrual is expected to be completed in 2024 with presentation of results in 2025. NCT05611931.

2024-06-03

Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study

To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus 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). Selinexor treatment was generally manageable, with no new safety signals identified. In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

Linked Investigators

Bradley J. Monk

Brian M. Slomovitz

Debra L Richardson

Giorgio Valabrega

Hannah C. Karpel

Ignace Vergote

Jacob Korach

J. Alejandro Pérez-Fidalgo

Jalid Sehouli

Director of the Department of Gynecology and Center of Oncological Surgery Head of the European Competence Center for Ovarian Cancer Deputy Director of the Charité Comprehensive Cancer Center Berlin in Germany

Mansoor Raza Mirza

Robert L. Coleman

Toon Van Gorp