Epcoritamab with rituximab + lenalidomide (r2) provides durable responses in high‐risk follicular lymphoma, regardless of pod24 status

Introduction: Follicular lymphoma (FL) is a heterogeneous disease. Early progression after initial treatment with chemoimmunotherapy, or POD24, occurs in approximately 20% of patients and strongly predicts poor outcomes. There is no standard treatment approach for patients with high-risk, relapsed or refractory (R/R) FL (high-risk subgroups in Table). Novel treatment options are needed to improve efficacy in patients with high unmet need. Epcoritamab, a subcutaneous 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: Patients with R/R CD20+ FL received subcutaneous epcoritamab + R2 for 12 cycles (28 d each). Epcoritamab was dosed QW in cycles 1–3, Q2W in cycles 4–9, and Q4W in cycles ≥10 (2a) or QW in cycles 1–2 and Q4W in cycles ≥3 (2b) for ≤2 y. Results: As of 31 October 2022, 109 R/R FL patients had received epcoritamab 48 mg + R2 in 2a and 2b. Median age was 65 y, 56% of patients had FLIPI 3–5, 61% had stage IV disease, and 59% had only 1 prior treatment line. 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 treatment. The most common treatment-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 cycle 1 day 15; all resolved and none led to discontinuation. ICANS occurred in 2 patients (G1, G2) and resolved. In 101 efficacy-evaluable patients, overall response rate (ORR) was 97%, with complete metabolic response (CMR) in 86%. Median time to any response and CMR was 1.4 mo. Estimated 6-mo progression-free survival was 93%. Notably, patients achieved higher ORR/CMR rates with epcoritamab + R2 versus their immediate prior treatment line (ORR, 97% vs. 85%; CMR, 86% vs. 60%). In second-line patients 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 patients with high-risk disease, suggesting subcutaneous epcoritamab 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). Encore Abstract—previously submitted to ASCO 2023 The research was funded by: This study was funded by Genmab A/S and AbbVie. Keywords: immunotherapy, indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract D. Belada Research funding: Genmab L. Falchi Consultant or advisory role: AbbVie, Genentech, Genmab, Roche, ADC Therapeutics, AstraZeneca, Seagen Research funding: AbbVie, Genentech, Genmab, Roche S. Leppä Consultant or advisory role: BeiGene, Genmab, Gilead, Incyte, Novartis, Orion, Roche Honoraria: Gilead, Incyte, Novartis Research funding: Bayer, Celgene, Genmab, Hutchmed, Novartis, Nordic Nanovector, Roche (Paid to Institution) H. Holte Consultant or advisory role: Incyte, Novartis, Roche, Takeda, Gilead, Roche Research funding: Incyte Other remuneration: Genmab, Nordic Nanovector: Safety Committee M. Hutchings Consultant or advisory role: AbbVie, Celgene, Genmab, Janssen, Roche, Takeda Research funding: Celgene, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, Takeda (All Paid to Institution) P. Lugtenburg Consultant or advisory role: Takeda, Servier: Research Grants; Celgene, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron Honoraria: Takeda, Servier: Research Grants; Celgene, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron P. Abrisqueta Consultant or advisory role: AbbVie, AstraZeneca, BMS, Janssen Other remuneration: AbbVie, AstraZeneca, BMS, Janssen: Speakers Bureau M. Nijland Consultant or advisory role: AbbVie Research funding: Nordic Nanovector, Takeda R. W. Merryman Consultant or advisory role: AbbVie, Adaptive Biotechnologies, BMS, Epizyme, Genmab, Intellia Research funding: BMS, Genentech/Roche, Genmab, Merck (All Paid to Institution) B. E. Wahlin Consultant or advisory role: Roche Research funding: Roche, Gilead Sciences K. M. Linton Consultant or advisory role: AbbVie, BeiGene, BMS, Celgene, Genmab, Kite/Gilead, Roche Research funding: AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Celgene, CellCentric, Genmab, Janssen, Kite/Gilead, MorphoSys, MSD, Nurix, Regeneron, Roche, Step Pharma, Viracta (All Paid to Institution) Educational grants: Celgene Other remuneration: Genmab: Member of the Epcoritamab Global Council; AbbVie, Celgene: Speakers Bureau L. Wang Employment or leadership position: Genmab A. Abbas Employment or leadership position: Genmab A. Rana Employment or leadership position: Genmab S. Quadri Employment or leadership position: AbbVie A. Sureda Consultant or advisory role: Takeda, BMS/Celgene, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite, Mundipharma, Bluebird Honoraria: Takeda, BMS/Celgene, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite Research funding: Takeda Educational grants: Takeda, BMS/Celgene, Roche Other remuneration: Takeda, BMS/Celgene, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite: Speakers Bureau.