Abstract
Introduction/Background Molecular characterization of patients with endometrial cancer (EC) has prognostic and therapeutic implications. Wild type TP53 (TP53wt) is found in ~75% of newly diagnosed EC and 50% of advanced/recurrent tumors; there are no targeted therapies for patients with TP53wt EC. Investigational selinexor is an oral XPO1 inhibitor that drives the nuclear retention and functional activation of wild type tumor suppressor proteins, such as p53. In the ENGOT-EN5/GOG-3055/SIENDO study (NCT03555422), preliminary analysis of a pre-specified exploratory subgroup of patients with TP53wt EC showed a decrease in risk for progression or death with a median PFS of 13.7 months with selinexor as maintenance therapy vs 3.7 months with placebo. Methodology XPORT-EC-042 (NCT05611931) is a phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of selinexor as maintenance therapy in patients with TP53wt primary stage IV or recurrent EC, who achieved a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing at least 12 weeks of platinum combination chemotherapy with or without immunotherapy. Among other inclusion/exclusion criteria, eligible patients must be ≥18 years of age, have histologically confirmed EC, and TP53wt tumor confirmed by NGS sequencing. Patients will be randomized 1:1 to receive selinexor 60mg PO or placebo once-weekly in 28-day cycles until progressive disease, toxicity, or 3-years if in complete response. A total of 220 patients are estimated to be enrolled globally. The primary endpoint is PFS based on RECIST v1.1 criteria as assessed by the Investigator. The key secondary endpoint is overall survival. Select secondary endpoints include safety assessments and PFS assessed by a blinded independent central review. Patient enrollment is ongoing. Results - Conclusion - Disclosures Ignace Vergote has received grants/research support from Oncoinvent AS (2019–2020) GRANT = CORPORATE SPONSORED RESEARCH -Amgen (2019–2020) -Roche (2019–2020); received honoraria or consulting fees from Agenus (2021) - Aksebio (2021) - Amgen (Europe) GmbH (2019) - AstraZeneca (2019–2022) - Bristol Myers Squibb (2021) - Clovis Oncology Inc. (2019–2019) -Carrick Therapeutics (2019) - Deciphera Pharmaceutials; and Accommodations, travel expenses (2019–2020) - Amgen - MSD - Tesaro - AstraZeneca - Roche. Mansoor Raza Mirza has received grants/research supports from AstraZeneca (Inst); Boehringer Ingelheim (Inst); Pfizer (Inst); Tesaro (Inst); honoraria or consultation fees from Honoraria - Advaxis; AstraZeneca; Cerulean Pharma; Clovis Oncology; Novocure; Pfizer; Roche; tesaro Consulting or Advisory Role - AstraZeneca; BioCad; Cerulean Pharma; Clovis Oncology; Genmab; Karyopharm Therapeutics; Novocure; Pfizer; Tesaro; Stock shareholder Karyopharm Therapeutics; SeraCare; and Leadership - Karyopharm Therapeutics; SeraCare; Travel Accommodations AstraZeneca; Karyopharm Therapeutics; Pfizer; Roche; SeraCare; Tesaro. Robert J Coleman has received grants/research supports from AstraZeneca/MedImmune( Institution), Clovis Oncology (Institution), Merck (Institution), Roche/Genentech (An Immediate Family Member), Immunogen (Institution), Mirati Therapeutics (Institution), Amgen (Institution), Pfizer (Institution), Lilly (Institution), Regeneron (Institution); honoraria or consultation fees Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, OncoMed, Immunogen, Abbvie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, GlaxoSmithKline, Eisai, GOG Foundation, Karyopharm Therapeutics; Stock shareholder McKesson; and Employement: US Oncology.Leadership: Onxeo. Travel, Accommodations, Expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Clovis Oncology, Sotio, Vaniam Group. Alejandro Pérez Fidalgo has received grants/research supports from Pharmamar and GSK (my institution); Participation in a company sponsored speaker’s bureau Astrazeneca, GSK, Clovis, Pharmamar (myself); and honoraria or consultation fees GSK, Clovis, Astrazeneca, Pharmamar, Roche. Bradley J Monk has received honorarium and consulting fees from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, Zentalis; and Speaker/Consultant AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, TESARO/GSK. Giorgio Valabrega has received Consulting or advisory: GSK, PharmaMar, Astrazeneca, MSD. Brian M. Slomovitz has received honoraria or consultation fees from AstraZeneca, Clovis, GSK, Genentech, Merck, Eisai, Lilly, Novartis, Genmab, Seagen, Immunogen, Karyopharm, Seagan. Toon Van Gorp has received grants/research supports fromAmgen, AstraZeneca, Roche; Advisory board (all payed to institute): AstraZeneca, Eisai, GSK, ImmunoGen, MSD, OncXerna, Seagen, Tubulis; Participation in a company sponsored speaker’s bureau GSK. Kathleen Moore has received grants/research supports from PTC Therapeutics, Merck, Lilly, Genentech/ROche, Verastem, GSK/Tesaro; honoraria or consultation fees Astra Zeneca, Alkemeres, Aravive, Addi, Blueprint pharma, Clovis, Eisai, EMD SErono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, Inxmed, Imab, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, OncXerna, OncoNova, VBL Therapeutics, Verastem; and serves as Associate Director for GOG Partners; receives royalties from Up to Date. Jalid Sehouli has Advisory Board, Personal, Invited Speaker GSK, MSD, PharmaMar, novocure, Tesaro, Astra Zeneca, Clovis, Eisei, Roche, Merck, Bayer, Molecular Health, Riemser instutional: Karyopharm, GSK, Astra Zeneca, Clovis, MSD, PharmaMar, Novartis, Tesaro, Novocure, MSD, Eisei, Roche Diagnostics, Molecular Health, Riemser. David Cibula has received honoraria from Roche Canada, GSK, Eisai, Merck; Consulting or advisory role Amgen and Eisai. Tally Levy has no conflicts of interest to disclose. Gerassimos Aravantionos received honoraria or consultation fees from Astrazeneca, Roche, BMS, and MSD. Kai Li and Pratheek Kalyanapu are employees of Karyopharm Therapeutics. Vicky Makker has received grants/research supports (Funding to institution) NIH/NCI Cancer Center Support Grant (P30 CA008748); and unpaid consultancy/unpaid advisory board membership from AstraZeneca, Clovis, Eisai, Faeth, Genentech, GSK, iTEOS, Novartis, Karyopharm, Moreo, MSD, Takeda, and Zymeworks. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.