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Regular and Young Investigator Award Abstracts
Clinical Trials Completed
370 Time course of treatment-related adverse events (TRAEs) during dostarlimab therapy in the GARNET trial
Free
  1. Bhavana Pothuri1,
  2. Dominique Berton2,
  3. Victor Moreno3,
  4. Ana Oaknin4,
  5. Jose Manuel Trigo Perez5,
  6. Giuseppe Curigliano6,
  7. Susan Ellard7,
  8. Joanna Pikiel8,
  9. Susana Banerjee9,
  10. Maria-Pilar Barretina-Ginesta10,
  11. Rowan Miller11,
  12. Anna Tinker12,
  13. Andrea Jewell13,
  14. Ruth Plummer14,
  15. Florence Joly15,
  16. Jennifer Veneris16,
  17. Tao Duan16 and
  18. Thierry Andre17
  1. 1Gynecologic Oncology Group (GOG) and Department of Obstetrics/Gynecology, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
  2. 2GINECO and Institut de Cancerologie de l’Ouest, Centre René Gauducheau, Saint-Herblain, France
  3. 3START Madrid-FJD, Fundación Jiménez Diaz Hospital, Madrid, Spain
  4. 4Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  5. 5Medical Oncology Department, Hospital Virgen de la Victoria IBIMA, Málaga, Spain
  6. 6Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, and University of Milano, Milan, Italy
  7. 7BC Cancer-Kelowna, British Columbia, Canada
  8. 8Regional Center of Oncology, Gdansk, Poland
  9. 9The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK
  10. 10Institut Català d’Oncologia, Hospital Universitari Dr. J. Trueta, Girona, Spain
  11. 11University College London, St. Bartholomew’s Hospital London, London, UK
  12. 12BC Cancer, Vancouver, British Columbia, Canada
  13. 13University of Kansas Medical Center, Kansas City, KS, USA
  14. 14Northern Institute for Cancer Research Medical School, University of Newcastle upon Tyne, London, UK
  15. 15Medical Oncology Department, Centre Francois Baclesse, Caen, France
  16. 16GlaxoSmithKline, London, UK
  17. 17Sorbonne University and Saint-Antoine Hospital, Paris, France

Abstract

Background Dostarlimab is a humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the ligands PD-L1 and PD-L2. Dostarlimab is approved as a monotherapy in adult patients (pts) with mismatch repair deficient (dMMR; US) or dMMR/microsatellite-instability high (EU) recurrent or advanced endometrial cancer that has progressed progressing on or following prior treatment with a platinum-containing regimen. GARNET is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in pts with solid tumors.

Methods Pts with dMMR solid tumors, mismatch repair proficient endometrial cancer, and non-small cell lung cancer that progressed on or after prior therapy received 500 mg of dostarlimab IV every 3 weeks (Q3W) for 4 cycles, then 1000 mg IV every 6 weeks (Q6W) for up to 2 years or until disease progression or discontinuation. Here, we report TRAEs by cycle.

Results A total of 515 pts were included. Of these pts, 60 (11.7%) experienced TRAEs leading to treatment interruption, and 25 (4.9%) experienced TRAEs leading to discontinuation. TRAEs of any grade with overall incidence of ≥10% of pts are shown (table 1). The majority of TRAEs occurred during cycles 1–3, with highest incidence during cycle 1. Grade 3 or 4 TRAEs were rare; those seen in ≥1% of pts are shown. Immune-related (ir) TRAEs of any grade with overall incidence of ≥2% of pts are shown. Most cases (96.9%) of irTRAEs occurred during cycles 1–8. The peak incidence of hypothyroidism occurred during cycle 4; in addition, frequency was increased during cycles 5–8, compared with cycles 1–4. No deaths were attributed to dostarlimab.

View this table:
Abstract 370 Table 1

Time course of adverse events in the GARNET trial

Conclusions No new safety signals were detected with dostarlimab compared to other anti–PD-1 inhibitors. Most TRAEs were low grade. The majority of TRAEs and grade ≥3 TRAEs occurred in the first 3 cycles (first 12 weeks), but some cases occurred later, suggesting a need for ongoing monitoring. Few increases in the incidence of TRAEs were seen during cycle 5 following the transition to the 1000-mg Q6W dosing schedule; the TRAEs with increased incidence after the transition were fatigue and lipase increased. An increase in the frequency of the irTRAE hypothyroidism was seen after transitioning to the 1000-mg Q6W schedule.

http://dx.doi.org/10.1136/jitc-2021-SITC2021.370

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