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  • 2022-RA-945-ESGO Antitumour activity of dostarlimab by PD-L1 and tumour mutation burden in patients with mismatch repair deficient and proficient tumours in the GARNET trial

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Translational research/biomarkers
2022-RA-945-ESGO Antitumour activity of dostarlimab by PD-L1 and tumour mutation burden in patients with mismatch repair deficient and proficient tumours in the GARNET trial
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  1. Susana Banerjee1,
  2. Thierry André2,
  3. Dominique Berton3,
  4. Susan L Ellard4,
  5. Begoña Jimenez5,
  6. Vanessa Samouëlian6,
  7. Lucy Gilbert7,
  8. Valentina Boni8,
  9. Xinwei Han9,
  10. Grace Antony10,
  11. Jennifer Veneris9 and
  12. Ana Oaknin11
  1. 1The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
  2. 2Sorbonne University and Saint-Antoine Hospital, Paris, France
  3. 3GINECO and Institut de Cancerologie de l’Ouest, Centre René Gauducheau, Saint-Herblain, France
  4. 4BC Cancer-Kelowna, Kelowna, BC, Canada
  5. 5Hospital Clínico Universitario Virgen de la Victoria, Malaga, Spain
  6. 6Gynecologic Oncology Division, Centre Hospitalier de l’Université de Montréal (CHUM), Centre de Recherche du CHUM (CRCHUM) et Université de Montréal, Montreal, QC, Canada
  7. 7Division of Gynecologic Oncology, McGill University Health Centre, Montreal, QC, Canada
  8. 8*affiliation at time of study. Current affiliation NEXT Oncology, Universitario Quironsalud, *START Madrid CIOCC (Centro Integral Oncológico Clara Campal), Hospital Universitario HM Sanchinarro, Madrid, Spain
  9. 9GSK, Waltham, MA
  10. 10GSK, London, UK
  11. 11Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

Abstract

Introduction/Background Dostarlimab is a programmed death 1 (PD-1) inhibitor approved as monotherapy in patients with mismatch repair deficient (dMMR) recurrent/advanced endometrial cancer (EC) that has progressed on or after platinum-based chemotherapy or solid tumours that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report a post hoc analysis of antitumour activity by PDL1 expression and tumour mutational burden (TMB) in patients with dMMR and MMR proficient (MMRp) solid tumours in the GARNET trial.

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Abstract 2022-RA-945-ESGO Table 1

Methodology GARNET (NCT02715284) is a phase 1, multicentre, open-label, single-arm study of dostarlimab in patients with advanced/recurrent solid tumours. Three expansion cohorts enrolled patients based on MMR status: dMMR (A1) and MMRp (A2) advanced/recurrent EC, and dMMR non-EC solid tumours (F). Patients received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg IV Q6W until progression or discontinuation. TMB and PDL1 were exploratory biomarkers. TMB status was determined by FoundationOne test; TMB-high (TMB-H) was defined as ≥10 mutations/Mb. PDL1 expression was determined by combined positive score (CPS) by Ventana assay; PDL1-high (PDL1-H) was defined as CPS ≥1. The study was not powered to assess antitumour activity within subgroups.

Results TMB-H and PDL1-H were common in dMMR solid tumours; PDL1-H was observed in 39.4% of MMRp EC tumours (table 1). Objective response rate (ORR) was higher in patients with TMB-H/PDL1-H tumours (55.6% for all cohorts, combined; Table). Safety for each cohort was previously reported.1

Conclusion PDL1-H and TMB-H were frequently observed in the dMMR EC and non-EC cohorts, regardless of tumour type; PDL1-H was also prevalent in MMRp EC tumours. Although not a powered analysis, ORR by BICR per RECIST v1.1 was higher in patients with TMB-H and PDL1-H solid tumours. Across cohorts, dMMR status was predictive of response.

Reference

  1. Andre T, et al. Ann Oncol 2021;32(suppl 5):S829-S866. 991P.

https://doi.org/10.1136/ijgc-2022-ESGO.878

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