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3110 Fixed-Duration Epcoritamab Plus Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Updated Results from Arm 1 of the Epcore NHL-5 Trial

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality)
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Ronit Gurion1*, Irit Avivi Mazza2*, Catherine Thieblemont, MD3, Won Seog Kim4*, Andras Masszi, MD, PhD5*, Alejandro Martín García-Sancho6*, Zsolt Nagy, MD, PhD7*, Benoit Tessoulin, MD, PhD8*, Ana Jimenez Ubieto9*, Po-Shen Ko, MD10*, Daniel Alan Kerr II, MD, PhD11*, Edwin E. Jeng, PhD12*, Satya Siddani, PhD12*, Neha Joshi, PhD12*, Neha Dixit, PhD12, Mariana Sacchi, MD13*, Pegah Jafarinasabian, MD, PhD12* and Abraham Avigdor, MD14

1Rabin Medical Center, Petah Tikva, and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2Hematology Division, Sourasky Medical Center and the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3Hôpital Saint-Louis, Hémato-oncologie, Université de Paris, Paris, France
4Samsung Medical Center, Seoul, Korea, Republic of (South)
5Orszagos Onkologiai Intezet, Budapest, Hungary
6Hospital Universitario de Salamanca, IBSAL, CIBERONC, Universidad de Salamanca, Salamanca, Spain
7Semmelweis Egyetem, Budapest, Hungary
8CHU de Nantes, Hotel Dieu, Paris, France
9Hospital Universitario 12 de Octubre, Madrid, Spain
10Taipei Veterans General Hospital Division of Hematology, Taipei, TWN
11Tampa General Hospital, Tampa, FL
12AbbVie Inc, North Chicago, IL
13Genmab, Plainsboro, NJ
14Sheba Medical Center, Ramat Gan, Israel

Introduction: Patients with relapsed or refractory (R/R) DLBCL have a poor prognosis, even if treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). CAR T therapy provides long-term remission in only 40% of patients, and some cannot receive CAR T therapy due to fitness, geographic, or financial limitations. Epcoritamab is a subcutaneous CD3×CD20 bispecific antibody approved for adults with R/R large B-cell lymphomas and follicular lymphoma after ≥2 lines of systemic therapy. Combining epcoritamab with lenalidomide provides a chemotherapy-free regimen that may enhance T-cell proliferation and augment natural killer cell activity, thereby increasing antitumor cytotoxicity. EPCORE NHL-5 (NCT05283720) is an ongoing, phase 1b/2, open-label, multi-arm, dose-escalation/expansion trial of epcoritamab in combination with antineoplastic agents for the treatment of non-Hodgkin lymphoma. Preliminary results from arm 1 of EPCORE NHL-5 demonstrated antitumor activity and tolerable safety in patients with R/R DLBCL treated with epcoritamab plus lenalidomide (Avivi Mazza, et al. Blood. 2023;142[Suppl1]:438). Here, we report updated results.

Methods: Eligible patients were ≥18 years old with CD20+ R/R DLBCL, had an Eastern Cooperative Oncology Group performance status of 0–2, were previously treated with at least 1 systemic therapy containing an anti-CD20 antibody, and were ineligible for or failed ASCT. Patients received epcoritamab (cycles 1–3, once weekly; cycles 4–12, once every 4 weeks) and oral lenalidomide (25 mg/day on days 1–21) for a total of twelve 28-day cycles. Epcoritamab was administered with two step-up doses in cycle 1: day 1, 0.16 mg; day 8, 0.8 mg; followed by 48 mg full dose from day 15 onward. Corticosteroid prophylaxis for cytokine release syndrome (CRS) was required during cycle 1. Key endpoints included dose-limiting toxicities (DLTs), investigator-assessed response (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), time to response, and safety.

Results: At the cutoff date of January 18, 2024, 40 patients received epcoritamab plus lenalidomide (60% male; median age 71.5 years, range, 26–85). Median (range) follow-up time was 11.5 (0.3–16.8) months. Among response-evaluable patients (n=37), ORR was 67.6%, with 51.4% of patients achieving a CR. Median DOR and CR have not been reached. Consistently high CR rates were observed across subgroups, including second-line patients (56.3%; n=16), patients who received prior CAR T (50%; n=10), and by molecular origin classification (GCB, 46.7%, n=15; ABC/non-GCB/unclassified, 46.7%, n=15). The safety profile was similar to that previously presented (Avivi Mazza, et al. Blood. 2023;142[Suppl1]:438). The most common grade 3–4 treatment-emergent adverse events (TEAEs) were neutropenia (60%), anemia (20%), thrombocytopenia (17.5%), and CRS (10%). Febrile neutropenia occurred in 2 patients (5%). Two patients (5%) experienced DLTs: CRS (Gr 3; n=1) and increased aspartate aminotransferase (Gr 4; n=1) during dose expansion. Overall, 65% of patients experienced CRS, mostly low grade: Gr 1: 14 (35%), Gr 2: 8 (20%), Gr 3: 4 (10%). Median onset of CRS was 16 days from the first dose (1 day after first full dose of epcoritamab) and all events resolved with a median time to resolution of 2 days. Immune effector cell–associated neurotoxicity syndrome occurred in 1 patient (2.5%; Gr 3), which resolved in 3 days. CRS rates and peak IL-6 levels were lower in patients receiving dexamethasone vs prednisone for CRS prophylaxis. There was 1 grade 5 TEAE considered related to epcoritamab of COVID-19 pneumonia. TEAEs leading to discontinuation of epcoritamab occurred in 4 (10%) patients (thrombocytopenia, n=2; COVID-19 pneumonia, n=1; pneumonia pneumococcal, n=1).

Conclusion: With longer follow-up, the combination of fixed-duration epcoritamab with lenalidomide continues to demonstrate deep and durable responses with a manageable safety profile for R/R DLBCL. CRS was predictable and mostly low grade; of note, most patients received prednisone vs the recommended dexamethasone for CRS prophylaxis. This chemotherapy-free combination may provide an alternative option to platinum-based or other standard of care therapies and thus supports the ongoing phase 3 trial of this combination for the treatment of R/R DLBCL (NCT06508658).

Disclosures: Gurion: Lilly: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Medison: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Avivi Mazza: Novartis: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Thieblemont: Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria; AstraZeneca: Honoraria; ADC Therapeutics: Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Cellectis: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations, Research Funding, Speakers Bureau; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel and Accommodation, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria; University of Paris: Current Employment, Ended employment in the past 24 months. Kim: Roche: Research Funding; Kyowa-Kirin: Research Funding; Donga: Research Funding; Boryong: Research Funding; BeiGene: Research Funding; Sanofi: Research Funding. Martín García-Sancho: Lilly: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and Accommodation Support; AstraZeneca: Consultancy, Honoraria; IDEOGEN: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: Travel and Accommodation Support; Kyowa Kirin: Consultancy, Honoraria; Roche: Honoraria, Other: Travel and Accommodation Support; Sobi: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Takeda: Honoraria; AbbVie: Consultancy, Honoraria; EUSA Pharma: Honoraria; BeiGene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel and Accommodation Support; Miltenyi Biotec: Consultancy, Honoraria; Novartis: Consultancy. Tessoulin: Lilly: Honoraria; Novartis: Honoraria; Gilead: Other: Travel Accommodations; AbbVie: Other: Travel Accommodations. Jimenez Ubieto: Gilead-Kite: Consultancy; Lilly: Consultancy; Regeneron: Speakers Bureau; Incyte: Speakers Bureau; Janssen: Other: Travel, Accommodations, and Expenses, Speakers Bureau; AbbVie: Other: Travel, Accommodations, and Expenses. Kerr: AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy; Incyte: Consultancy; BeiGene: Speakers Bureau. Jeng: AbbVie: Current Employment, Other: stockholder of AbbVie. Siddani: AbbVie: Current Employment, Other: stockholder of AbbVie. Joshi: AbbVie: Current Employment, Other: stockholder of AbbVie. Dixit: AbbVie: Current Employment, Other: Owns AbbVie stock. Sacchi: Genmab: Current Employment, Current equity holder in publicly-traded company, Other: owns Genmab stock. Jafarinasabian: AbbVie: Current Employment, Other: stockholder of AbbVie. Avigdor: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Karyospharm: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; TG Therapeutics: Consultancy; Ascentage: Consultancy, Honoraria, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau.

*signifies non-member of ASH