Interim analysis of the immune-related endpoints of the mismatch repair deficient (dMMR) and proficient (MMRp) endometrial cancer cohorts from the GARNET study

Abstract

<h3>Objectives:</h3> Dostarlimab is a humanized programmed death (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 (pts) with solid tumors. Here, we report efficacy endpoints by irRECIST based on investigator assessment (IA) for the endometrial cancer (EC) cohorts. <h3>Methods:</h3> This is a multicenter, open-label, single-arm, dose-escalation and cohort-expansion study. Here, we report on 2 independent expansion cohorts of pts with recurrent or advanced EC (dMMR EC and MMRp EC, determined by immunohistochemistry [IHC]) that progressed on or after a platinum-based chemotherapy regimen. Pts received 500 mg dostarlimab IV Q3W for 4 cycles, then 1000 mg Q6W until disease progression, discontinuation, or withdrawal. The primary endpoints of objective response rate (ORR) and duration of response (DOR) by blinded independent central review (BICR) using RECIST v1.1, and safety have been reported previously.1 Immune-related endpoints (irORR and irDOR by irRECIST) are based on IA, and are prespecified secondary endpoints. <h3>Results:</h3> In total, 126 dMMR and 145 MMRp pts identified by IHC were enrolled and dosed. Of these, 103 dMMR and 142 MMRp pts had measurable disease at baseline by BICR, and sufficient follow-up time (6 mo) for the primary efficacy analyses. 110 dMMR and 144 MMRp pts had measurable disease at baseline by IA and sufficient follow-up time (6 mo) and were included for efficacy analysis of irORR and irDOR; some additional pts were considered to have measurable disease at baseline by IA. Efficacy data based on irRECIST are shown in the table. irORR was 45.5% in dMMR pts, and 13.9% in MMRp pts. <h3>Conclusions:</h3> Efficacy endpoints reported by RECIST v1.1 and irRECIST show similar results. irDCR was particularly of interest in the MMRp cohort, a group with a poorer prognosis. The potential benefit seen in this single-arm trial awaits confirmation in ongoing randomized controlled studies. <b>Reference:</b> [1] Oaknin, A, et al. Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325. LBA36. <h3>Funding:</h3> GlaxoSmithKline.