Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Dostarlimab in advanced/recurrent (A/R) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC): the GARNET study  (#218)

Ana Oaknin 1 , Bhavana Pothuri 2 , Lucy Gilbert 3 , Renaud Sabatier 4 , Sharad Ghamande 5 , Adriano Gravina 6 , Emiliano Calvo 7 , Susana Banerjee 8 , Niamh Mangan 9 , Rowan E Miller 10 , Joanna Pikiel 11 , Mansoor R Mirza 12 , Tao Duan 13 , Sybil Zildjian 14 , Eleftherios Zografos 15 , Jennifer Veneris 14 , Anna V Tinker 16
  1. Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  2. Gynecologic Oncology Group (GOG) and Department of Obstetrics/Gynecology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York City, USA
  3. Division of Gynecologic Oncology, McGill University Health Centre, Montreal, Quebec, Canada
  4. Department of Medical Oncology, Institut Paoli Calmettes, Aix-Marseille University, Marseille, France
  5. Department of Obstetrics & Gynecology, Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
  6. Clinical Trial Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy
  7. START Madrid–CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain
  8. Gynaecology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
  9. GSK, Melbourne, Australia
  10. University College London, St. Bartholomew’s Hospitals London, London, UK
  11. Department of Chemotherapy, Regional Center of Oncology, Gdansk, Poland
  12. Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Denmark, Nordic Society of Gynaecologic Oncology–Clinical Trial Unit, Copenhagen, Denmark
  13. GSK, Pennington, New Jersey, USA
  14. GSK, Waltham, Massachusetts, USA
  15. GSK, London, UK
  16. Department of Medicine, British Columbia Cancer, Vancouver Centre, University of British Columbia, Vancouver, Canada

Aims Dostarlimab is a PD-1 inhibitor approved provisionally in Australia as monotherapy for patients with dMMR A/R EC that has progressed on/after a platinum-containing regimen. Efficacy and safety in two expansion cohorts of the multicenter, open-label, single-arm Phase I GARNET trial are reported (third interim analysis).

Methods Patients with A/R EC were assigned to Cohort A1 (dMMR/MSI-H) or A2 (MMRp/MSS);receiving dostarlimab 500 mg IV Q3W X4, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. Primary endpoints were ORR and DOR by blinded independent central review (RECIST v1.1).

Results 153 dMMR/MSI-H and 161 MMRp/MSS patients were enrolled/dosed; 143 and 156 patients were in the efficacy-evaluable population, respectively (measurable disease at baseline; ≥6 months follow-up). ORRs (95% CI) were 45.5% (37.1–54.0; dMMR/MSI-H) and 15.4% (10.1–22.0; MMRp/MSS). Median (m) DOR (95% CI) was not reached (NR) (1.18+ to 47.21+; dMMR/MSI-H) and 19.4 months (2.80–47.18+; MMRp/MSS). 6-, 9-, and 12-month PFS was 49.5%, 48.0%, and 46.4% in dMMR/MSI-H EC and 35.8%, 31.3%, and 29.4% in MMRp/MSS EC, respectively. mOS (95% CI) was NR (25.7–NR; dMMR/MSI-H) and 16.9 months (13.0–21.8; MMRp/MSS).

27 patients (8.6%) discontinued treatment because of a treatment-related adverse event (TRAE). The majority of TRAEs were Grade 1/2; most common any-Grade TRAEs were fatigue (56; 17.8%), diarrhea (46; 14.6%), and nausea (43; 13.7%). No deaths were attributed to dostarlimab. Hypothyroidism (12; 8%) was the most common any-Grade immune-related TRAE.

Conclusions Dostarlimab demonstrated durable antitumor activity in A/R EC. dMMR/MSI-H was associated with higher ORR and longer PFS/OS. Safety was consistent with other PD-1 antibodies.

Funding GSK (213346 [NCT02715284]). ©2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved. Presented on behalf of original authors with permission. 10.1200/JCO.2022.40.16_suppl.5509–5509.