Deep and Durable Responses with Epcoritamab SC Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma: Data from the Epcore NHL-1 Follicular Lymphoma Dose-Expansion Cohort

Background An unmet need exists for effective, well-tolerated, and convenient treatment (tx) options in patients (pts) with high-risk relapsed/refractory (R/R) follicular lymphoma (FL), including double refractory pts (refractory to anti-CD20 tx and an alkylating agent) and pts with disease progression within 2 y of first-line (1L) immunochemotherapy (POD24). Epcoritamab, a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved in the US for adults with R/R diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic tx. We present initial results from the FL dose-expansion cohort of the EPCORE™ NHL-1 trial (NCT03625037; phase 1/2). Methods Pts with CD20+ R/R FL (grade [G] 1–3A) with ≥2 prior systemic tx lines received epcoritamab SC in 2 step-up doses in cycle (C) 1, followed by full 48-mg doses in 28-d Cs: QW, C1–3; Q2W, C4–9; and Q4W, C≥10 until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed per Lugano criteria by IRC. Minimal residual disease (MRD) was assessed using NGS in peripheral blood. Results Between Sep 2020 and Oct 2022, 128 pts with R/R FL G1–3A were enrolled. As of Apr 21, 2023, the median follow-up was 17.4 mo. Median age was 65 y, 61% of pts had FLIPI 3–5, and 85% had stage III–IV disease. The median number of prior lines of tx was 3 (range, 2–9). Most pts were primary refractory (54%), double refractory (70%), or refractory to their last prior tx (69%); 42% had POD24, and 52% progressed within 2 y of initiating any 1L tx. The ORR was 82%, with a complete response (CR) rate of 63% (Figure). Median time to response/CR was 1.4/1.5 mo. ORRs/CR rates were consistently high across prespecified subgroups: double refractory, 76%/56%; refractory to last prior tx, 74%/51%; POD24, 80%/61%; progression within 2 y of initiating any 1L tx, 79%/64%. Median progression-free survival (PFS) was 15.4 mo; median duration of response, duration of CR, and overall survival were not reached. MRD negativity was correlated with improved PFS. The most common any-grade tx-emergent AEs (TEAEs) were CRS (66%), injection-site reaction (57%), COVID-19 (40%), and fatigue (30%). TEAEs leading to tx discontinuation occurred in 19% of pts, most commonly COVID-19. CRS was mostly low grade (40% G1, 25% G2, 2% G3), primarily occurred following the first full dose (median time to onset after first full dose, 15 h), and did not lead to tx discontinuation. There was clinically meaningful reduction in CRS incidence and severity in a separate R/R FL cohort evaluating an optimized SUD regimen in C1. Conclusions In hard-to-treat, high-risk pts with R/R FL, epcoritamab SC monotherapy resulted in deep, durable responses with a manageable safety profile. High ORR/CR rates were consistent across subgroups, and a correlation between MRD negativity and PFS was observed.