Subcutaneous epcoritamab induces deep, durable complete remissions in relapsed/refractory large b‐cell lymphoma: longer follow‐up from the pivotal epcore nhl‐1 trial

Introduction: Outcomes are poor for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Effective treatments that drive deep, durable responses and long-term benefit are needed. In the pivotal EPCORE™ NHL-1 trial (NCT03625037), single-agent epcoritamab showed high complete response (CR) and MRD-negativity rates and a manageable safety profile as an off-the-shelf, subcutaneous, CD3xCD20 T-cell–engaging bispecific antibody (Thieblemont et al. J Clin Oncol, 2022). We present updated results, including longer follow-up, in a challenging-to-treat population. Methods: Patients with R/R CD20+ LBCL received subcutaneous epcoritamab (step-up priming and intermediate doses followed by 48-mg full doses) in 28-d cycles: QW, cycles 1–3; Q2W, cycles 4–9; Q4W, cycles ≥10 until PD or unacceptable toxicity. Results: As of 18 November 2022, of 157 patients (median age, 64 y) with LBCL (including DLBCL [n = 139; 12/88 double/triple-hit by FISH], HGBCL [n = 9], PMBCL [n = 4], and FL grade 3B [n = 5]), 36 remain on study treatment. Patients had a median of 1.6 y from initial diagnosis to first dose and a median of 3 (range, 2–11) prior treatment lines; 61% of patients had primary refractory disease, and 39% had prior CAR T, of whom 75% progressed within 6 mo of treatment. Median follow-up was 20 mo (range, 0.3+ to 28.2). Patients received a mean of 9.1 cycles. LBCL overall response and CR rates were 63.1% and 39.5%, respectively, and were consistent for DLBCL (61.9% and 39.6%, respectively). The median duration of CR was 20.8 mo. Median time to CR was 2.7 mo; 8 patients converted from partial response to CR at ≥36 wk. Median overall survival was 18.5 mo (95% CI, 11.7–not reached [NR]) for patients with LBCL and 19.4 mo (95% CI, 11.7–NR) for patients with DLBCL. Median overall survival was NR in patients who achieved CR. Additional outcomes for patients with CR are shown in the Table. The most common treatment-emergent AEs of any grade (G) were CRS (51%), neutropenia (24%), pyrexia (24%), fatigue (23%), nausea (22%), and diarrhea (21%). Nine patients (6%) had G1–2 ICANS, and 1 patient had a G5 event with confounding factors. Fatal treatment-emergent AEs occurred in 15 patients; 2 were considered related (COVID-19, ICANS). CRS was predominantly low grade (48% G1–2; 3% G3) and occurred following the first full dose (cycle 1, day 15). One patient discontinued treatment due to G1 CRS. Conclusions: These data with longer follow-up reaffirm single-agent subcutaneous epcoritamab induces durable CRs with improved outcomes and a manageable safety profile in patients with R/R LBCL. No new safety signals were observed in these hard-to-treat patients. These impressive data support the ongoing phase 3 studies evaluating epcoritamab across different lines of treatment and in various combinations. Encore Abstract—previously submitted to ASCO 2023 This study was funded by Genmab A/S and AbbVie Keywords: aggressive B-cell non-Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract C. Thieblemont Consultant or advisory role: AbbVie, Amgen, BMS/Celgene, Cellectis, Gilead Sciences, Kite, Novartis, Roche, Incyte, Janssen, Takeda Honoraria: AbbVie, Amgen, Bayer, Cellectis, Gilead Sciences, Incyte, Janssen, Kite, Novartis, Takeda Research funding: BMS/Celgene, Hospira, Roche Educational grants: AbbVie, Amgen, BMS/Celgene, Cellectis, Gilead Sciences, Kite, Novartis, Roche W. Jurczak Consultant or advisory role: Janssen, AstraZeneca, MEI Pharma, Lilly, Takeda, Roche, AbbVie, BeiGene Research funding: AbbVie, Bayer, BeiGene, Celgene, Janssen, Roche, Takeda, TG Therapeutics, AstraZeneca, MEI Pharma, Lilly C. Y. Cheah Consultant or advisory role: Roche, Janssen, MSD, Gilead, Ascentage Pharma, AstraZeneca, Lilly, TG Therapeutics, BeiGene, Novartis, BMS Honoraria: Roche, Janssen, MSD, Gilead, Ascentage Pharma, AstraZeneca, Lilly, TG Therapeutics, BeiGene, Novartis, BMS Educational grants: BMS, Roche, AbbVie: Research Funding; Roche M. R. Clausen Consultant or advisory role: AbbVie, Janssen, Gilead, AstraZeneca, Genmab Educational grants: AbbVie, Janssen, AstraZeneca, Genmab D. Cunningham Research funding: MedImmune/AstraZeneca, Clovis, Lilly, 4SC, Bayer, Celgene, Roche (All Paid to Institution, Royal Marsden Hospital) D. J. Lewis Consultant or advisory role: Janssen, Lilly, Roche, BeiGene, Kite R. Gasiorowski Honoraria: MSD, Otsuka, Novartis, Astellas, Janssen, AbbVie, Takeda T. M. Kim Consultant or advisory role: AstraZeneca, Boryung, F. Hoffmann-La Roche Ltd/Genentech, Janssen, Novartis, Sanofi, Takeda, Yuhan Research funding: AstraZeneca-KHIDI (Outside This Work) T. Feldman Consultant or advisory role: AbbVie, AstraZeneca, Epizyme, Genmab, Gilead/Kite, Karyopharm, Takeda, Seagen Other remuneration: Speakers Bureau: Seagen 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 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 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) A. Cottereau Other remuneration: Genmab: Payments for PET Reviews, Made to a Research Account M. Cota Stirner Employment or leadership position: AbbVie Y. Liu Employment or leadership position: Genmab N. Kilavuz Employment or leadership position: Genmab M. Sacchi Employment or leadership position: Genmab P. Lugtenburg Honoraria: Celgene, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron Research funding: Takeda, Servier H. Ghesquieres Consultant or advisory role: Gilead Sciences, Celgene, Janssen, Roche, Mundipharma, Takeda Honoraria: Gilead Sciences, Celgene, Janssen, Roche, Mundipharma, Takeda