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  • 272 Dostarlimab in advanced/recurrent mismatch repair deficient/microsatellite instability high or proficient/stable endometrial cancer: the GARNET study

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Endometrial cancer
272 Dostarlimab in advanced/recurrent mismatch repair deficient/microsatellite instability high or proficient/stable endometrial cancer: the GARNET study
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  1. A Oaknin1,
  2. L Gilbert2,
  3. AV Tinker3,
  4. J Brown4,
  5. C Mathews5,
  6. J Press6,
  7. R Sabatier7,
  8. DM O’malley8,
  9. V Samouëlian9,
  10. V Boni10,
  11. L Duska11,
  12. S Ghamande12,
  13. P Ghatage13,
  14. R Kristeleit14,
  15. C Leath15,
  16. J Veneris16,
  17. T Duan16,
  18. E Im16 and
  19. B Pothuri17
  1. 1Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  2. 2McGill University Health Centre Research Institute, Montreal, Quebec, Canada
  3. 3BC Cancer, Vancouver, British Columbia, Canada
  4. 4Division of Gynecologic Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
  5. 5Women and Infants Hospital of Rhode Island, Providence, RI, USA
  6. 6Swedish Cancer Institute Gynecologic Oncology and Pelvic Surgery, Seattle, WA, USA
  7. 7Department of Medical Oncology, Institut Paoli Calmettes, Aix-Marseille University, Marseille, France
  8. 8The Ohio State University – James Comprehensive Cancer Center, Columbus, OH, USA
  9. 9Gynecologic Oncology Service, Department of Obstetrics and Gynecology, CHUM, Université de Montréal, Montreal, Quebec, Canada
  10. 10START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, Madrid, Spain
  11. 11Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA, USA
  12. 12Georgia Cancer Center, Augusta University, Augusta, GA, USA
  13. 13Department of Gynecological Oncology, University of Calgary, Calgary, Alberta, Canada
  14. 14Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK
  15. 15O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
  16. 16GlaxoSmithKline, Waltham, MA, USA
  17. 17New York University, Department of Obstetrics and Gynecology, NYU Langone Health, Perlmutter Cancer Center, New York, NY, USA

Abstract

Introduction/Background*Dostarlimab is a humanised programmed death (PD-1) receptor monoclonal antibody approved for patients with mismatch mutation repair-deficient/microsatellite instability-high (dMMR/MSI-H) recurrent or advanced endometrial cancer (EC) that progressed on or after a platinum-based chemotherapy regimen. GARNET is a phase 1 study assessing the antitumour activity and safety of dostarlimab monotherapy in patients with advanced solid tumours.

Methodology GARNET is a multicentre, open-label, single-arm study. Here we report on 2 independent expansion cohorts of patients with recurrent or advanced EC that progressed on or after a platinum-based chemotherapy regimen. Patients were assigned to cohort A1 (dMMR/MSI-H EC) or cohort A2 (mismatch mutation repair-proficient/microsatellite-stable [MMRp/MSS] EC) based on immunohistochemistry testing. Patients received 500 mg of dostarlimab intravenously once every 3 weeks for 4 cycles, then 1000 mg once every 6 weeks until disease progression, discontinuation or withdrawal. The primary endpoints are objective response rate (ORR) and duration of response by blinded independent central review using RECIST version 1.1.

Result(s)*In total, 129 dMMR/MSI-H and 161 MMRp/MSS patients were enrolled and dosed. Of these, 108 dMMR/MSI-H and 156 MMRp/MSS patients who had measurable disease at baseline and ≥6 months of follow-up were included for efficacy analyses. ORR and disease control rate (DCR) for dMMR/MSI-H EC was 43.5% and 55.6%, respectively; ORR and DCR for MMRp/MSS EC was 14.1% and 34.6%, respectively (table 1). Overall, 16 patients (5.5%) discontinued treatment due to a treatment-related adverse event (5 dMMR/MSI-H, 11 MMRp/MSS). Table 2 shows safety by cohort and overall. No deaths were attributed to dostarlimab.

View this table:
Abstract 272 Table 1

Antitumour activity

View this table:
Abstract 272 Table 2

Most common adverse events

Conclusion*Dostarlimab demonstrated durable antitumour activity in both dMMR/MSI-H and MMRp/MSS advanced/recurrent EC. dMMR/MSI-H status was associated with a higher response rate. DCR achieved in MMRp/MSS EC was noteworthy, considering MMRp/MSS tumours are historically associated with a poor prognosis. The dostarlimab safety profile was manageable.

Clinical trial registration NCT02715284

https://doi.org/10.1136/ijgc-2021-ESGO.131

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