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1737 Efficacy and Safety of Epcoritamab Monotherapy in Patients with Relapsed or Refractory LBCL Not Previously Exposed to CAR T: Subanalysis of the Epcore NHL-1 Trial

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Adult, Lymphomas, Non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell lymphoma, Diseases, Aggressive lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Yasmin H. Karimi, MD1, Michael Roost Clausen, MD, PhD2*, David John Lewis, MD3*, Wojciech Jurczak, MD, PhD4, Michelle Poon, MBBS, MRCP5*, Tae Min Kim, MD, PhD6*, Young Rok Do, MD, PhD7, Pieternella Lugtenburg, MD, PhD8, Kristin Conte, MPH9*, David Soong, PhD10*, Barbara D'Angelo Månsson, PhD11*, Zhu Li, MS10*, Christian Eskelund, MD, PhD10* and Martin Hutchings, MD, PhD12

1Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI
2Vejle Hospital, Vejle, Denmark
3University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
4MSC National Research Institute of Oncology, Kraków, Poland
5Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore
6Seoul National University Hospital, Seoul, Korea, Republic of (South)
7Keimyung University Dongsan Medical Center, Daegu, Korea, Republic of (South)
8On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Erasmus MC Cancer Institute, University Medical Center, Department of Hematology, Rotterdam, Netherlands
9AbbVie, North Chicago, IL
10Genmab, Plainsboro, NJ
11Genmab, Copenhagen, Denmark
12Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

Introduction: Although chimeric antigen receptor T-cell therapies (CAR T) are approved in the relapsed or refractory (R/R) large B-cell lymphoma (LBCL) setting, their usage may be limited by patient (pt) eligibility/fitness, accessibility, and/or manufacturing timelines and consistency. Epcoritamab, a subcutaneous (SC) CD3xCD20 T‑cell–engaging bispecific antibody available off the shelf, has led to deep, durable responses with manageable toxicity in pts with R/R LBCL in the pivotal phase 2 EPCORE® NHL-1 trial (NCT03625037), and is approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma (FL) after ≥2 prior lines of therapy. Epcoritamab has also been shown to be effective in pts post CAR T (overall response rate [ORR]/complete response [CR] rate: 54%/34%; Phillips et al, ASH 2022). Here, we report efficacy and safety results from a subanalysis of pts not previously treated with CAR T (CAR T naive) in the EPCORE NHL-1 trial.

Methods: Adult pts with R/R CD20+ LBCL (including diffuse LBCL [DLBCL], high‑grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and FL grade 3B) and ≥2 prior lines of systemic antilymphoma therapy were treated with epcoritamab SC (2 step-up doses followed by 48-mg full doses) in 28‑d cycles. Pts were treated QW, cycles 1–3; Q2W, cycles 4–9; and Q4W, cycles ≥10, until progressive disease or unacceptable toxicity. Corticosteroid prophylaxis was used during cycle 1. The primary endpoint was ORR per Lugano criteria. Minimal residual disease (MRD) was evaluated using the clonoSEQ® (Adaptive Biotechnologies) ctDNA assay.

Results: A total of 96 CAR T–naive pts with R/R LBCL were treated with epcoritamab. Median age was 69 y (range, 31–83 [median age in the total R/R LBCL population (N=157), 64 y]) and 60% were male. The median number of prior lines of therapy was 3 (range, 2–11), and 50 pts (52%) had ≥3 prior lines. At data cutoff (May 3, 2024), 13 pts (14%) remained on epcoritamab; the most common reasons for treatment discontinuation were progressive disease in 52 pts (54%) and adverse events in 22 pts (23%). The ORR and CR rate per investigators were 61% and 45% (median study follow-up, 37.3 mo [range, 0.3+ to 45.5]). Median duration of response was 18.4 mo (95% CI, 9.7–30.4). Median duration of CR was 28.6 mo (95% CI, 15.8 to not reached [NR]) and an estimated 46% remained in CR at 36 mo. Median progression-free survival (PFS) was 4.3 mo (95% CI, 3.4–10.9) overall and 33.3 mo (95% CI, 19.4–NR) among complete responders. Median overall survival (OS) was 15.4 mo (95% CI, 11.0–27.8) overall and NR (95% CI, 27.8–NR) among complete responders. At 36 mo, an estimated 40% of pts overall and 83% of complete responders had not initiated their next antilymphoma therapy. Among 35 pts who received subsequent antilymphoma therapy, 10/35 (29%) received CAR T; 6 of these 10 pts remain alive at data cutoff. Of 74 MRD-evaluable pts, 33 (45%) were MRD negative. In a cycle 3 day 1 landmark analysis, estimated 36-mo rates of PFS/OS were 42%/52% among MRD-negative pts and 16%/31% among MRD-positive pts. The most common treatment‑emergent AEs (TEAEs) were cytokine release syndrome (CRS; 60%), diarrhea (24%), pyrexia (23%), fatigue (22%), neutropenia (22%), and injection-site reaction (21%). Fatal TEAEs were reported in 18 pts; 9 of 18 events were related to COVID‑19. TEAEs led to treatment discontinuation in 22 pts (23%) and were most commonly COVID-19 pneumonia (8%), COVID-19 (3%), and pneumonia (2%). CRS events were mostly grade 1 (33%) or grade 2 (23%); 4% of pts had grade 3 CRS. CRS was most common following the first full (cycle 1 day 15) dose (median time to onset, 20 h). CRS resolved in all but 2 pts and led to treatment discontinuation in 1 pt. ICANS occurred in 7 pts (7%; grade 1, 6%; grade 5, 1%). Clinical tumor lysis syndrome occurred in 2 pts (2%; each grade 3). Immunoglobulin G levels decreased by a median of ~20% after the start of epcoritamab treatment (baseline median: 653.0 mg/dL) and remained stable over time.

Conclusions: With over 3 years of follow-up, single-agent epcoritamab demonstrated deep and durable responses and manageable side effects in CAR T–naive pts with R/R LBCL, as demonstrated by this subgroup analysis. Results were consistent with those seen in the overall EPCORE NHL-1 LBCL population, considering differences in baseline characteristics, and show that epcoritamab can be administered safely and effectively before or after CAR T for the treatment of R/R LBCL.

Disclosures: Karimi: AstraZeneca: Research Funding; Lilly/Loxo: Research Funding; Merck: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Xencor: Research Funding; Roche/Genentech: Other: Travel Expenses, Research Funding. Clausen: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Other: Travel Expenses; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Incyte: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel Expenses; Pfizer: Other: Travel Expenses. Lewis: Janssen, Lilly, Roche, BeiGene, Kite, Astrazeneca: Consultancy, Honoraria. Jurczak: Janssen Cilag: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; MSD: Research Funding; Lilly: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding. Kim: Takeda: Consultancy, Honoraria; Regeneron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Samsung Bioepis: Consultancy; Amgen: Consultancy, Honoraria; Daiichi Sankyo, HK inno.N, F. Hoffmann-La Roche Ltd/Genentech, Yuhan: Consultancy; Yuhan: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Roche/Genetech: Consultancy; IMBDx. Inc.: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Boryung: Consultancy; AstraZeneca/MedImmune: Consultancy. Lugtenburg: Y-mAbs Therapeutics: Other: Consultancy Honoraria; BMS, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron, Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda, Servier: Research Funding. Conte: AbbVie: Current Employment. Soong: Genmab: Current Employment, Current equity holder in publicly-traded company. D'Angelo Månsson: Genmab: Current Employment. Li: Genmab: Current Employment. Eskelund: Genmab: Current Employment. Hutchings: BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Incyte: Research Funding; Janssen/J&J: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.

*signifies non-member of ASH