Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study

ABSTRACT

Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy;and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Results: 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached;estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusions: Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification NCT02715284. Editorial acknowledgement Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure A.V. Tinker Financial Interests, Institutional, Sponsor/Funding: AstraZeneca;Financial Interests, Personal, Other AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK;Financial Interests, Personal, Other Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners;Financial Interests, Personal, Advisory Board Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray;Financial Interests, Personal, Leadership Role GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro;Financial Interests, Personal, Other Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier Financial Interests, Institutional, Funding: AstraZeneca, Eisai;Financial Interests, Personal, Other AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche;Non-Financial Interests, Personal, Other AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown Financial Interests, Personal, Advisory Role Caris, Clovis, Eisai, GlaxoSmithKline;Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande Financial Interests, Personal, Advisory Role Seattle Genetics;Financial Interests, Personal, Speaker’s Bureau GlaxoSmithKline;Financial Interests, Institutional, Funding: Abbv e, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews Financial Interests, Institutional, Research Grant Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics;Financial Interests, Personal, Advisory Board IMAB biopharma. D. O'Malley Financial Interests, Personal, Advisory Board AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp;Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI);Financial Interests, Personal, Other Myriad Genetics, Tarveda. V. Boni Financial Interests, Personal, Advisory Board OncoArt, Guidepoint Global;Financial Interests, Personal, Speaker’s Bureau Solti;Financial Interests, Personal, Other START, Loxo, IDEAYA Biosciences;Financial Interests, Institutional, Research Grant Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina Financial Interests, Personal, Other Gentili, Pfizer. S. Banerjee Financial Interests, Personal, Advisory Board Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna;Financial Interests, Personal, Invited Speaker Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview;Financial Interests, Personal, Stocks/Shares PerciHealth;Financial Interests, Institutional, Research Grant AstraZeneca, GSK, Tesaro;Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201 Verastem;Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored) Astrazeneca;Non-Financial Interests, Advisory Role Epsilogen;Non-Financial Interests, Other, Member of membership committee ESGO;Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity Ovacome Charity;Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated) Lady GardenFoundation Charity. R. Miller Financial Interests, Personal, Other AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline;Financial Interests, Personal, Speaker’s Bureau AZD, Clovis Oncology, GSK, Roche. J. Pikiel Financial Interests, Personal, Other Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza Financial Interests, Personal, Advisory Board AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab;Financial Interests, Personal, Invited Speaker AstraZeneca, GSK, Karyopharm;Financial Interests, Personal, Stocks/Shares Karyopharm;Financial Interests, Institutional, Research Grant GSK, AstraZeneca, ultimovacs, Apexigen;Financial Interests, Institutional, Invited Speaker Deciphera;Non-Financial Interests, Advisory Role Ultimovacs, Apexigen. T. Duan Financial Interests, Personal, Full or part-time Employment GlaxoSmithKline. G. Antony Financial Interests, Personal, Fu l or part-time Employment GlaxoSmithKline. S. Zildjian Financial Interests, Personal, Full or part-time Employment GlaxoSmithKline. E. Zografos Financial Interests, Personal, Full or part-time Employment GlaxoSmithKline. J. Veneris Financial Interests, Personal, Full or part-time Employment GlaxoSmithKline. A. Oaknin Financial Interests, Personal, Advisory Board AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,;Financial Interests, Personal, Other, Travel and accomodation AstraZeneca, PharmaMar, Roche;Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb;Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair GEICO;Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO GCIG;Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines. ESMO;Non-Financial Interests, Member ESMO, ASCO, GCIG, SEOM, GOG.