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2022-RA-1194-ESGO Efficacy of dostarlimab in endometrial cancer by molecular subtype: a post hoc analysis of the GARNET study
  1. Anna V Tinker1,
  2. Bhavana Pothuri2,
  3. Lucy Gilbert3,
  4. Renaud Sabatier4,
  5. Jubilee Brown5,
  6. Sharad Ghamande6,
  7. Cara Mathews7,
  8. David M O’Malley8,
  9. Valentina Boni9,
  10. Adriano Gravina10,
  11. Susana Banerjee11,
  12. Rowan E Miller12,
  13. Joanna Pikiel13,
  14. Mansoor R Mirza14,
  15. Tao Duan15,
  16. Xinwei Han16,,
  17. Sybil Zildjian16,,
  18. Eleftherios Zografos17,
  19. Jennifer Veneris16 and
  20. Ana Oaknin18
  1. 1Department of Medicine, British Columbia Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada
  2. 2Gynecologic Oncology Group (GOG) and Department of Obstetrics/Gynecology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY
  3. 3Division of Gynecologic Oncology, McGill University Health Centre, Montreal, QC, Canada
  4. 4Department of Medical Oncology, Institut Paoli Calmettes, Aix-Marseille University, Marseille, France
  5. 5Division of Gynecologic Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC
  6. 6Department of Obstetrics and Gynecology, Georgia Cancer Center, Augusta University, Augusta, GA
  7. 7Women and Infants Hospital of Rhode Island, Providence, RI
  8. 8Division of Gynecologic Oncology and Gynecologic Oncology Phase I Program, The Ohio State University and the James Cancer Center, Columbus, OH
  9. 9NEXT Oncology Hospital Universitario Quirónsalud Madrid, Madrid, Spain
  10. 10Clinical Trial Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy
  11. 11Gynaecology Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
  12. 12University College London, St. Bartholomew’s Hospitals London, London, UK
  13. 13Department of Chemotherapy, Regional Center of Oncology, Gdansk, Poland
  14. 14Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Denmark, Nordic Society of Gynaecologic Oncology-Clinical Trial Unit, Copenhagen, Denmark
  15. 15GSK, Pennington, NJ
  16. 16GSK, Waltham, MA
  17. 17GSK, London, UK
  18. 18Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain ed. †Employed by GSK at the time the study was conduct, tudy was START Madrid CIOCC. *Current affiliation; affiliation at the time of s


Introduction/Background Biomarkers are used to classify endometrial cancer (EC) into molecular subtypes such as TCGA and/or a surrogate classification (POLε mutated [mut], mismatch repair/microsatellite instability [MMR/MSI], TP53mut, and no specific mutation profile [NSMP]) or by estrogen receptor (ER) status. Here, we report on a post hoc analysis of objective response rate (ORR) by a surrogate classification for EC in patients receiving dostarlimab monotherapy.

Methodology GARNET is a multicentre, open-label, single-arm phase 1 study. Patients were assigned to cohort A1 (MMR deficient/MSI-high [dMMR/MSI-H EC]) or A2 (MMR proficient/microsatellite stable [MMRp/MSS] EC) based on local assessment. Patients received 500 mg of dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints were ORR and duration of response by blinded independent central review. Molecular subtype was determined by POLε and TP53 mutation status by Foundation Medicine, and MMR/MSI status was determined by local immunohistochemistry or next-generation sequencing; all others were assigned as NSMP. The hierarchy for classification was POLεmut → MMR/MSI → TP53 status → NSMP. ER status was determined by local immunohistochemistry testing. Only patients with samples available for additional biomarker testing were included in the biomarker assessment.

Results 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS were included in the efficacy-evaluable population. ORRs were determined for molecular subtypes and ER expression (table 1). Safety has been previously reported.

Abstract 2022-RA-1194-ESGO Table 1

Conclusion The observed ORRs in each molecular subgroup were consistent with the overall ORR in each cohort. Differences by ER expression status were not observed. These findings support the importance of testing patients with EC for MMR/MSI biomarker status as a predictor of response. Additionally, data suggest that TP53 mutation or ER expression should not modify treatment approach. The data are of interest for hypothesis generation.

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