187 Selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: long-term follow up of efficacy and safety subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study

Jalid Sehouli; Ignace Vergote; Erika Hamilton; Alejandro Pérez Fidalgo; Toon Van Gorp; Giovanni Scambia; Jaroslav Klat; Tally Levy; Stephen Welch; Debra L Richardson; Eva Maria Guerra Alía; Stéphanie Henry; Pauline Wimberger; David S Miller; Jerónimo Martínez; Bradley J Monk; Pratheek Kalyanapu; Monsoor Raza Mirza; Vicky Makker

doi:10.1136/ijgc-2024-ESGO.20

Abstract

Introduction/Background As the treatment landscape evolves, molecular characterization is important to inform treatment decisions for patients with endometrial cancer (EC). Wild type TP53 (TP53wt) is found in >50% of advanced/recurrent EC, of those, 40–55% are microsatellite stable (pMMR [MSS]). Currently, there is limited evidence of benefit for these molecular subgroups with available treatments.

Methodology ENGOT-EN5/GOG-3055/SIENDO (NCT03555422) is a randomized, double-blind, phase 3 trial evaluating selinexor versus placebo as maintenance treatment for advanced/recurrent EC following response to prior systemic therapy. Here we report updated efficacy and safety of a prespecified exploratory subgroup analysis of patients with TP53wt EC.

Results 113 patients with TP53wt EC received selinexor (n=77) or placebo (n=36) as maintenance therapy. As of September 1, 2023, median follow-up was 28.9 months; 23 patients remain on treatment. Median PFS (mPFS) was 27.4 months with selinexor versus 5.2 months with placebo (HR 0.41; 95% CI [0.25–0.69], nominal one-sided p=0.0002). PFS improvement was observed regardless of microsatellite stability status; in the TP53wt/pMMR (MSS) subgroup, the mPFS was not reached with selinexor versus 4.9 months with placebo. Although overall survival data are immature, an encouraging trend was observed in the TP53wt population HR 0.76 (95%CI 0.36–1.59). A similar trend was observed in the TP53wt/pMMR (MSS) subgroup (HR 0.57; [95% CI: 0.24–1.35]). (figure 1)

In patients with TP53wt, most common adverse events (AEs) were nausea, vomiting, and diarrhea; rates of diarrhea were comparable between treatment arms; 16% of patients discontinued selinexor due to AEs. One treatment-emergent AE leading to death occurred in the placebo group.

Abstract 187 Figure 1

Conclusion TP53wt status may represent a robust predictive biomarker for selinexor efficacy in EC. Additionally, a strong PFS signal and encouraging OS signal was observed regardless of microsatellite stability status, and particularly in the TP53wt/pMMR (MSS) subgroup, a patient population with high unmet need.

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. 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. Erika Hamilton has received grants/research supports from

(Made to institution) Abbvie Acerta Pharma ADC Therapeutics AKESOBIO Australia Amgen Aravive

ArQule Arvinas AstraZeneca AtlasMedx Black Diamond Boehringer Ingelheim Clovis Compugen

Curis CytomX Daiichi Sankyo Dana Farber Cancer Inst Deciphera eFFECTOR Therapeutics Ellipses

Pharma EMD Serono Fochon FujiFilm G1 Therapeutics H3 Biomedicine Harpoon Hutchinson

MediPharma Immunogen Immunomedics Incyte InvestisBio Jacobio Karyopharm Leap Therapeutics

Lilly Lycera Mabspace Biosciences Macrogenics MedImmune Merck Mersana Merus Millennium

Molecular Templates Myraid Genetic Laboratories Novartis Nucana Olema OncoMed Onconova

Therapeutics ORIC Pharmaceuticals Orinove Pfizer PharmaMar Pieris Pharmaceuticals Pionyr

Immunotherapeutics Plexxikon Radius Health Regeneron Repertoire Immune Medicine Rgenix

Roche/Genentech Seattle Genetics Sermonix Pharmaceuticals Shattuck Labs Silverback StemCentRx

Sutro Syndax Syros Taiho TapImmune Tesaro Treadwell Therapeutics Verastem Vincerx Pharma

Zenith Epigenetics Zymeworks; and Consulting/Advisory role (made to institution) : Arcus Arvinas

AstraZeneca Black Diamond Boehringer Ingelheim CytomX Daiichi Sankyo Dantari Deciphera

Pharmaceuticals Eisai H3 Biomedicine iTeos Janssen Lilly Loxo Merck Mersana Novartis Pfizer Puma

Biotechnology Relay Therapeutics Roche/Genentech Seattle Genetics Silverback Therapeutics. Giorgio

Valabrega has received consulting or advisory fee from GSK, PharmaMar, astrezeneca, MSD, and

Eisai. 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. 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. Jaroslav Klat has no conflicts of interest to disclose. Tally Levy has no conflicts of interest to disclose. Stephen Welch has received

Honoraria: Roche Canada, GSK, Pfizer, Eisai, Merck. Consulting or advisory role: Amgen, Eisai.

Debra L Richardson has received fees for Advisory Board: Mersana, GlaxoSmithKline. Advisory board participant and moderator: AstraZeneca. Eva Maria Guerra Alía has received fees for

Advisory/consultancy: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche;

Speaker bureau/expert testimony: AstraZeneca, PharmaMar, Roche, GSK; and

Travel/accommodation/expenses: Roche, TESARO: A GSK Company and Baxter. Giovanni Scambia has received fees for grants/research supports from MSD Italia S.r.l.; Consultant: TESARO Bio Italy

S.r.l. Johnson & Johnson; and Speakers Bureau/Honoraria: Clovis Oncology Italy S.r.l.. Stéphanie

Henry has received fees for honoraria or consultation AstraZeneca, Merck, Novartic, MSD Oncology,

BMSi, Sanofi, Gelead, GSK; and Travel, Accommodations, Expenses: Roche, MSD, GSK, Teva.

Pauline Wimberger has received fees for Honoraria, Astrazeneca, MSD, Eisai, Novartis, Roche,

Amgen, Pfizer Clovis, Gilead, Lilly. Consulting or advisory role, Astrazeneca, MSD, Eisai, Novartis,

Pfizer, Roche, Amgen, Clovis, Lilly, Gilead, GSK. Funded research, Amgen, AstraZeneca, MSD,

Novartis, Pfizer, Roche, GSK, Clovis. David Miller has received fees for Consulting or adisory: genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Karyopharm Therapeutics,

Incyte, Janssen, Alexion Pharmaceuticals, Clovis Oncology, Asymmetric Therapeutics, LLC, Boston

Biomedical, Research Institute, Tarveda Therapeutics, Myriad Genetic Laboratories Inc,

GlaxoSmithKline LLC, AbbiVie Inc, EMD Serono Inc, Seagen Inc, Clinical Education Alliance LLC,

Eisai Europe Limited, iTeos Belgium SA, Novocure Inc, Novartis. Jerónimo Martínez has received fees for Advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro,

PharmaMar; Speaker bureau/expert testimony honorarium from PharmaMar, GSK-Tesaro, Clovis; and

Travel/accommodation/expenses from PharmaMar, GSK-Tesaro. 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. Pratheek Kalyanapu is an employee of Karyopharm

Therapeutics. 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 - KaryopharmIgnace Vergote has received grants/research support from Oncoinvent AS (2019–2020) GRANT =