549P - Progression-free survival (PFS) and overall survival (OS) in patients (pts) with mismatch repair deficient (dMMR) solid tumors treated with dostarlimab in the GARNET study

Background

Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in pts with dMMR/microsatellite instability–high advanced/recurrent endometrial cancer (EC) that has progressed on or after platinum-based treatment; and in the US as a monotherapy in pts with dMMR advanced/recurrent EC that has progressed on or after platinum-based treatment 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 pts with dMMR solid tumors from 2 expansion cohorts of the GARNET trial.

Methods

GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR EC) or cohort F (dMMR non-EC solid tumors) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab intravenously 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

For the third interim analysis, 356 pts with dMMR solid tumors were enrolled and treated. The efficacy-evaluable population included 327 pts with dMMR solid tumors with measurable disease at baseline who enrolled on or before June 1, 2021, to allow sufficient follow-up time to assess response. Median follow-up was 27.7 mo for dMMR solid tumors (Table). Overall median PFS was 6.9 mo with 3-year estimated PFS rate of 39.7%. With 38.8% maturity, overall dMMR solid tumor median OS was not reached, and 3-year estimated OS was 55.9%. Safety for both cohorts has been previously reported. Table: 549P

Datacut: 1 Nov 2021.
dMMR, mismatch repair deficient; EC, endometrial cancer; NR, not reached; OS, overall survival; PFS, progression-free survival

Conclusions

Dostarlimab demonstrated durable antitumor activity and favorable PFS and OS in dMMR solid tumors, including EC, gastrointestinal, and other tumor types. The secondary endpoints demonstrate the benefit of dostarlimab in pts with dMMR solid tumors, in line with the primary endpoints previously reported.

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, Waltham, MA, USA.

Disclosure

T. André: Financial Interests, Personal, Advisory Board: Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis, Gritstone Oncology, GlaxoSmithKline, Haliodx, Kaleido Biosciences, Merck & Co., Inc, Pierre Fabre, Roche/Ventana, Sanofi, Seagen, Servier, Transgene; Financial Interests, Personal, Other: Roche/Genentech, MSD & Co, Bristol-Myers Squibb. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory Board: Exact Science, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai; Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche, Bristol Myers Squibb. A.V. Tinker: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other: AstraZeneca, Eisai. 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. F.G.M. De Braud: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis, Incyte, BMS, Menarini; Financial Interests, Personal, Speaker’s Bureau: BMS, Healthcare Research & Pharmacoepidemiology, Merck Group, ACCMED, Nadirex, MSD, Pfizer, Servier, Sanofi, Roche, AMGEN, Incyte. S. Ellard: Financial Interests, Personal, Stocks/Shares: GlaxoSmithKline. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier, Guardant; Financial Interests, Personal, Advisory Board: iOnctura, Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. J.M. Trigo Perez: Financial Interests, Institutional, Funding: AstraZeneca, MSD; Financial Interests, Personal, Other: AstraZeneca, MSD, BMS, Takeda, Boehringer. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline; Financial Interests, Institutional, Funding: GlaxoSmithKline, Genentech. 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, Full 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. 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. All other authors have declared no conflicts of interest.