Epcoritamab + R2 regimen and responses in high-risk follicular lymphoma, regardless of POD24 status.

Abstract

7506 Background: Follicular lymphoma (FL) is a heterogeneous disease. Early progression after initial treatment (tx) with chemoimmunotherapy (CIT), POD24, occurs in around 20% of patients (pts) and strongly predicts poor outcomes. There is no standard tx approach for high-risk, relapsed or refractory (R/R) FL (high-risk subgroups in Table). Novel options are needed to improve efficacy in pts with high unmet need. Epcoritamab, a subcutaneous (SC) T-cell–engaging bispecific antibody, demonstrated impressive single-agent antitumor activity and a manageable safety profile in R/R FL (Hutchings et al, Lancet 2021) and shows promise combined with standards of care. Here we present pooled analyses from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE NHL-2 trial (NCT04663347) of epcoritamab with rituximab + lenalidomide (R2). Methods: Pts with R/R CD20+ FL received epcoritamab SC + R2 for 12 cycles (Cs; 28 d each). Epcoritamab was dosed QW in C1–3, Q2W in C4–9, and Q4W in C≥10 (2a) or QW in C1–2 and Q4W in C≥3 (2b) for ≤2 y. Results: As of Oct 31, 2022, 109 R/R FL pts had received epcoritamab 48 mg + R2 in 2a and 2b. Median age was 65 y, 56% of pts had FLIPI 3–5, 61% had stage IV disease, and 59% had only 1 prior tx. Most had received alkylating agents (92%) or anthracyclines (62%); 2 had prior CAR T. At a median follow-up of 8.8 mo (range, 1.2–18.5), 82% were still on tx. The most common tx-emergent AEs were: CRS and neutropenia, 48% each; injection-site reactions, 38%; and fatigue, 33%. CRS events were mostly low grade (G; 46% G1–2, 2% G3) and mostly occurred following the first full dose on C1D15; all resolved and none led to discontinuation. ICANS occurred in 2 pts (G1, G2) and resolved. In 101 efficacy-evaluable pts, overall response rate (ORR) was 97%, with complete metabolic response (CMR) in 86%. Notably, pts achieved higher ORR/CMR rates with epcoritamab + R2 vs their immediate prior tx line (ORR, 97% vs 85%; CMR, 86% vs 60%). Estimated 6-mo progression-free survival was 93%. In second-line (2L) pts with POD24, ORR/CMR rates were 95%/90% (additional high-risk subgroup data in Table). Additional data with longer follow-up will be presented. Conclusions: Epcoritamab + R2 showed potent antitumor activity and a manageable safety profile in a large R/R FL population. Encouraging responses were seen in pts with high-risk disease, suggesting epcoritamab SC may abrogate negative effects of high-risk features. A separate POD24 cohort is planned, and epcoritamab + R2 is being studied in the phase 3 EPCORE FL-1 trial (NCT05409066). Clinical trial information: NCT04663347 . [Table: see text]