83 Time course of adverse events during dostarlimab treatment in patients with recurrent or advanced endometrial cancer in the garnet trial

Introduction/Background* Dostarlimab is a humanized programmed death-1 (PD-1) receptor monoclonal antibody that blocks interaction with the PD-1 ligands. GARNET (NCT02715284) is a phase 1 study assessing antitumor activity and safety of dostarlimab monotherapy in patients with solid tumors. Dostarlimab has shown antitumor activity in patients with mismatch repair deficient (dMMR) and mismatch repair proficient (MMRp) advanced and recurrent endometrial cancer (EC). Here we report on the time of onset of treatment-related adverse events (TRAEs) and immune-related (ir) TRAEs over the course of dostarlimab treatment in patients with dMMR (cohort A1) and MMRp (cohort A2) EC in the GARNET trial. Methodology Patients with advanced or recurrent dMMR or MMRp EC that progressed on or after a platinum regimen received 500 mg of dostarlimab every 3 weeks for 4 cycles, then 1000 mg every 6 weeks (Q6W) until disease progression or discontinuation. Result(s)* A total of 126 patients with dMMR EC and 145 patients with MMRp EC were included in the safety population. Few TRAEs were seen in ≥10% of patients: fatigue (17.3%), diarrhea (14.4%), nausea (13.7%), and asthenia (11.1%). The majority of cases occurred during cycles 1–3, with a peak occurrence at cycle 1 for all 4 TRAEs. Hypothyroidism was the only irTRAE seen in ≥5% of patients, and 94% of cases occurred between cycles 2 and 8, with a peak occurrence seen at cycle 4. irTRAEs that were seen in ≥1% of patients included diarrhea (4.1%), amylase increased (2.2%), aspartate aminotransferase increased (2.2%), alanine aminotransferase increased (1.8%), colitis (1.5%), hyperglycemia (1.5%), lipase increased (1.5%), adrenal insufficiency (1.1%), and hyperthyroidism (1.1%). Conclusion* When analyzed over the dMMR and MMRp EC safety population of the GARNET trial, dostarlimab has an acceptable safety profile with manageable adverse events. irTRAEs and TRAEs were seen in a low percentage of patients and were seen more frequently earlier in the time course of dostarlimab treatment. No increase in the rate of TRAEs or irTRAEs was seen when changing to the 1000-mg Q6W dose. C, cycle; dMMR, mismatch mutation repair deficient; ir, immune-related; MMRp, mismatch mutation repair proficient; TRAE, treatment-related adverse event; W, weeks