IBCL-1332: Phase 3 Results From the EPCORE FL-1 Trial of Epcoritamab With Lenalidomide and Rituximab vs Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Context: Epcoritamab (E) is a CD3 × CD20 bispecific antibody approved for R/R FL after ≥2 pLOT. E + lenalidomide and rituximab (R 2 ) showed 97% ORR (CRR, 87%) and manageable safety in the phase 1b/2 EPCORE NHL-2 trial (Falchi ASH 2024). EPCORE FL-1 is a phase 3 trial of fixed-duration E+R 2 vs R 2 in patients with 2L+ FL (NCT05409066). Objective: Report EPCORE FL-1 results. Design: Adults with CD20 + FL R/R after ≥1 pLOTwere randomized to E+R 2 or R 2 for ≤12 cycles (C). E was administered subcutaneously (2- or 3-step-up dose [3SUD] to 48 mg in C1; C1–3, weekly; C4–12, every 4 weeks) with oral lenalidomide (C1–12, days 1–21) and intravenous rituximab (C1, weekly; C2–5, every 4 weeks). Patients received mandatory C1 CRS prophylaxis. Dual primary endpoints: ORR and PFS. Secondary endpoints: CRR, OS, DOR/DOCR, and safety. Results: The primary endpoints were met, showing E+R 2 superiority over R 2 in ORR and PFS. As of 5/24/2025, 488 patients were randomized (E+R 2 n=243; R 2 n=245). Patient characteristics were generally well-balanced. Median follow-up was 14.8 months (95% CI, 14.1–15.5 months). ORR (95% CI) was higher with E+R 2 (95% [92%–97%]) vs R 2 (79% [74%–84%]; P < 0.0001); 12-month DOR (95% CI) was 89.2% (83.6%–93.0%) vs 48.5% (38.8%–57.5%). Compared with R 2 E+R 2 demonstrated longer PFS (HR, 0.21 [95% CI, 0.14–0.31]; P < 0.0001) and higher CRR (83% [95% CI, 77%–87%] vs 50% [95% CI, 43%–56%]; P < 0.0001). CRS occurred in 26% of E+R 2 3SUD patients (grade [G]1, 21%; G2, 5%), mostly at E first 48-mg dose; all resolved. TEAEs were higher with E+R 2 vs R 2 (G3/4 TEAEs, 90% vs 67%; G3/4 neutropenia, 69% vs 42%; G3/4 infections, 33% vs 15%; G3/4 febrile neutropenia, 6% vs 3%; TEAEs leading to discontinuation, 19% vs 12%). Fatal TEAEs occurred in 2% (n = 4) vs 4% (n = 9) (none related to E). Conclusions: E+R 2 demonstrated superiority over R 2 in R/R FL, with significantly improved ORR, CRR, and PFS. G3/4 neutropenia and infections were higher with E+R 2 but manageable and not fatal. CRS was low-grade with predictable timing. E+R 2 sets a new benchmark as an option suitable for outpatient administration and potential new 2L+ FL SOC. CD: cluster of differentiation, CRR: complete response rate, CRS: cytokine release syndrome, DOCR: duration of complete response, DOR: duration of response, FL: follicular lymphoma, HR: hazard ratio, ORR: objective response rate, PFS: progression-free survival, pLOT: prior lines of therapy, RR: relapsed/refractory, SOC: standard of care, TEAE: treatmentemergent adverse event. Bradley D Hunter presenting on behalf of the EPCORE FL-1 study investigators. The data were previously published (Falchi et al . Lancet . 2026;407:161–173) and reproduced with permission under the terms of the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Authors: Bradley D Hunter, Lorenzo Falchi, Marcel Nijland, Huiqiang Huang, Kim M Linton, John F Seymour, Rong Tao, Michal Kwiatek, Abel Costa, Theodoros P Vassilakopoulos, Richard Greil, Ana Jiménez-Ubieto, Shane Gangatharan, Ohad Benjamini, Catherine Thieblemont, Alessandra Tucci, Anna Elinder-Camburn, Arpad Illes, Jan Novak, Miguel Pavlovsky, Andrew McDonald, Dok Hyun Yoon, Yuko Mishima, Gauri Sunkersett, JP Mei, Nabanita Mukherjee, Feng Zhu, Elena Favaro, Franck Morschhauser
Institutions: Intermountain Healthcare, LDS Hospital, Memorial Sloan Kettering Cancer Center, University Medical Center Groningen, University of Groningen, Sun Yat-sen University, University of Manchester, The Christie NHS Foundation Trust, Cancer Research UK Manchester Centre, The Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Fudan University, Fudan University Shanghai Cancer Center, D’Or Institute for Research and Education, National and Kapodistrian University of Athens, Laiko General Hospital of Athens, Paracelsus Medical University, Hospital Universitario 12 De Octubre, Fiona Stanley Hospital, Sheba Medical Center, Hôpital Saint-Louis, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, North Shore Hospital, University of Debrecen, University Hospital Kralovske Vinohrady, Fundación para la Investigación, Docencia y Prevención del Cáncer, Asan Medical Center, University of Ulsan, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, AbbVie (United States), Genmab (Denmark), Hôpital Claude Huriez
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,890
OpenAlex ID: W7204683096
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