549P Progression-free survival (PFS) and overall survival (OS) in patients (pts) with mismatch repair deficient (dMMR) solid tumors treated with dostarlimab in the GARNET study

Abstract

Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in pts with dMMR/microsatellite instability–high advanced/recurrent endometrial cancer (EC) that has progressed on or after platinum-based treatment; and in the US as a monotherapy in pts with dMMR advanced/recurrent EC that has progressed on or after platinum-based treatment or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in pts with dMMR solid tumors from 2 expansion cohorts of the GARNET trial. GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR EC) or cohort F (dMMR non-EC solid tumors) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab intravenously every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. For the third interim analysis, 356 pts with dMMR solid tumors were enrolled and treated. The efficacy-evaluable population included 327 pts with dMMR solid tumors with measurable disease at baseline who enrolled on or before June 1, 2021, to allow sufficient follow-up time to assess response. Median follow-up was 27.7 mo for dMMR solid tumors (Table). Overall median PFS was 6.9 mo with 3-year estimated PFS rate of 39.7%. With 38.8% maturity, overall dMMR solid tumor median OS was not reached, and 3-year estimated OS was 55.9%. Safety for both cohorts has been previously reported.Table: 549PdMMR ECN=141dMMR non-EC solid tumorsN=186Overall dMMR solid tumN=327Median follow-up, mo27.629.827.7Median PFS (95% CI), mo5.6 (4.1–16.6)7.0 (3.6–16.5)6.9 (4.2–13.6)Estimated probability of PFS, %12 mo24 mo36 mo46.039.639.645.641.439.645.840.639.7OS maturity, %39.038.738.8Median OS (95% CI), moNR (25.7–NR)NR (21.7–NR)NR (31.6–NR)Estimated probability of survival, %12 mo24 mo36 mo71.259.457.069.657.955.070.358.655.9Datacut: 1 Nov 2021. dMMR, mismatch repair deficient; EC, endometrial cancer; NR, not reached; OS, overall survival; PFS, progression-free survival Open table in a new tab Datacut: 1 Nov 2021. dMMR, mismatch repair deficient; EC, endometrial cancer; NR, not reached; OS, overall survival; PFS, progression-free survival Dostarlimab demonstrated durable antitumor activity and favorable PFS and OS in dMMR solid tumors, including EC, gastrointestinal, and other tumor types. The secondary endpoints demonstrate the benefit of dostarlimab in pts with dMMR solid tumors, in line with the primary endpoints previously reported.