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342 Fixed-Duration Epcoritamab + R2 Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Novel Treatment Strategies and New Data on Old Standards for Follicular Lymphoma
Hematology Disease Topics & Pathways:
Combination therapy, Adult, Research, Clinical trials, Non-Hodgkin lymphoma, Bispecific Antibody Therapy, Lymphomas, B Cell lymphoma, Clinical Research, Indolent lymphoma, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Human, Study Population
Saturday, December 7, 2024: 5:15 PM

Lorenzo Falchi, MD1, Anna Sureda Balari, MD, PhD2, Sirpa Leppä, MD PhD3*, Joost S.P. Vermaat4, Marcel Nijland, MD, PhD5*, Jacob Haaber Christensen, MD, PhD6*, Sven de Vos, MD, PhD7*, Harald Holte, MD, PhD8, Reid W. Merryman, MD9, Pieternella Lugtenburg, MD, PhD10, Pau Abrisqueta Costa, MD, PhD11*, Kim Linton12*, Gauri Sunkersett, DO13*, Christopher Morehouse, MS14*, Andrew J. Steele, PhD14*, Jennifer Marek14*, Liwei Wang, PhD14*, Daniela Hoehn, MD, PhD14*, Martin Hutchings, MD, PhD15 and David Belada, MD, PhD16

1Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
2Clinical Hematology Department, Institut Català d’Oncologia – L’Hospitalet, IDIBELL, Universitat de Barcelona, Barcelona, Spain
3University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
4Leiden University Medical Center, Leiden, Netherlands
5University Medical Center Groningen and University of Groningen, Groningen, Netherlands
6Odense University Hospital, Odense, Denmark
7Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA
8Oslo University Hospital and KG Jebsen Center for B-cell Malignancies, Oslo, Norway
9Dana-Farber Cancer Institute, Boston, MA
10On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Erasmus MC Cancer Institute, University Medical Center, Department of Hematology, Rotterdam, Netherlands
11Hospital Universitario Vall d’Hebro, Barcelona, Spain
12The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
13AbbVie, North Chicago, IL
14Genmab, Plainsboro, NJ
15Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
164th Department of Internal Medicine – Hematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic

Introduction: Epcoritamab, a CD3xCD20 bispecific antibody, has been approved as a single agent for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma and follicular lymphoma (FL) after ≥2 lines of systemic therapy based on results from the phase 1/2 EPCORE® NHL-1 trial (NCT03625037). For patients (pts) with R/R FL, rituximab + lenalidomide (R2) is an approved and widely accepted regimen based on results from the AUGMENT trial (overall response rate [ORR], 78%; complete response [CR] rate, 34%; estimated 2-y progression-free survival [PFS], 58%). There exists a clear need for improvement of outcomes, especially for pts with high-risk features, including disease progression within 24 mo of first-line chemoimmunotherapy (POD24) or primary/double-refractory disease, for whom there is no established standard of care. Previously, in arm 2 of the EPCORE NHL‑2 trial (phase 1b/2; NCT04663347), fixed-duration epcoritamab + R2 showed encouraging antitumor activity and a manageable safety profile in a large population of pts with R/R FL, including high-risk pts (Merryman et al, ASCO 2023). Here, we present long-term follow-up beyond 2 y and minimal residual disease (MRD) analysis for the first time.

Methods: Adults with R/R CD20+ FL received subcutaneous epcoritamab + R2 for up to 12 cycles (Cs; 28 d each). Epcoritamab was administered with a 2-step (0.16 and 0.8 mg) step-up dosing (SUD) regimen in C1 and 48-mg full doses either QW in C1–3, Q2W in C4–9, and Q4W in C≥10 (arm 2a) or QW in C1–2 and Q4W in C≥3 (arm 2b) for up to 2 y. MRD analysis was performed on peripheral blood mononuclear cell samples collected at prespecified time points (clonoSEQ® assay, Adaptive Biotechnologies) and quantified as tumor clones detected per 1 x 106 nucleated cells. The primary endpoint was ORR per Lugano criteria.

Results: As of May 15, 2024, 111 pts with R/R FL had received epcoritamab 48 mg + R2. Median age was 65 y, 61% had stage IV disease, and 57% had only 1 line of prior treatment. Most pts had received alkylating agents (93%) and anthracyclines (64%); 3% had received prior CAR T. At a median follow-up of 25.3 mo (range, 2.4+ to 34.1), 17 pts (15%) were still on treatment, 41 (37%) completed treatment per protocol, and 53 (48%) discontinued treatment (progressive disease, n=18; AEs, n=22; pt withdrawal, n=7; death, n=1; COVID-19 control measure, n=1; and other reason, n=4 [investigator decision]).

The ORR was 96%, and CR rate was 87%. CR rates were similarly high regardless of high-risk features: primary refractory (n=39)/non–primary refractory (n=72), 90%/86%; double refractory (n=39)/non–double refractory (n=72), 82%/90%; POD24 (n=42)/non-POD24 (n=69), 79%/93%. Estimated 24-mo PFS and overall survival rates were 70% and 90%, respectively. At 24 mo, an estimated 69% of responders remained in response (duration of response; DOR), and an estimated 75% of complete responders remained in CR (duration of CR; DOCR). MRD status was assessed in 73 evaluable pts; of these, 64 (88%) became MRD negative.

With the majority of pts being enrolled and treated during the global COVID-19 pandemic, COVID-19 was reported in 57% of pts and led to epcoritamab discontinuation in 11% of pts; COVID-19 events included 5 grade (G) 5 treatment-emergent AEs (TEAEs; COVID-19, n=3; COVID-19 pneumonia, n=2). The other most common TEAEs were neutropenia (62%) and CRS (51%). CRS events with this 2-step SUD regimen were mostly low grade (38% G1, 12% G2, 2% G≥3) and primarily occurred following the first full dose on C1D15; all resolved, and none led to epcoritamab discontinuation. ICANS occurred in 1 pt (G1) and resolved.

Conclusions: With more than 2 y of follow-up, fixed-duration epcoritamab + R2 continued to show deep and durable responses (CR rate, 87%; estimated 24-mo DOCR, 75%) in pts with R/R FL, irrespective of high-risk features. Considering limitations of cross-trial comparisons, these results (estimated 2-y PFS, 70%) compare favorably with those reported for R2 alone in the AUGMENT trial (estimated 2-y PFS, 58%). The depth of responses was underscored by MRD negativity in 88% of evaluable pts. There were no new safety findings, and the safety profile remained consistent with previous reports. Epcoritamab + R2 is being studied further in the ongoing, randomized, phase 3 EPCORE FL-1 trial (NCT05409066).

Disclosures: Falchi: Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees; EvolveImmune: Consultancy; Roche: Consultancy, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Research Funding; Taylor Francis: Other: Journal Editor; Kaplan: Other: CME Presentation: Projects in Knowledge. Sureda Balari: EBMT: Other: President; GETH-TC: Other: President; GSK: Consultancy, Honoraria, Speakers Bureau; Takeda Pharmaceutical: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Mundipharma: Consultancy; Alexion: Honoraria; Roche: Honoraria, Other: Travel Expenses; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees. Leppä: BeiGene, Genmab, Gilead, Incyte, Novartis, Orion, Roche: Membership on an entity's Board of Directors or advisory committees; Bayer, BMS, Genmab, Hutchmed, Novartis, Nordic Nanovector, Roche: Research Funding; Gilead, Incyte, Novartis: Honoraria. Vermaat: Secura Bio: Consultancy. Holte: SERB: Consultancy; Incyte: Consultancy; Pierre Fabre: Consultancy. Merryman: Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DG Medicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Merck: Research Funding. Lugtenburg: Takeda, Servier: Research Funding; BMS, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron, Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Y-mAbs Therapeutics: Other: Consultancy Honoraria. Costa: AbbVie, AstraZeneca, BMS, Janssen: Consultancy, Speakers Bureau. Linton: AbbVie: Consultancy, Research Funding, Speakers Bureau; CellCentric: Research Funding; Janssen: Research Funding; Regeneron: Research Funding; Step Pharma: Research Funding; AstraZeneca: Research Funding; MSD: Research Funding; MorphoSys: Research Funding; Celgene: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Consultancy, Research Funding; Genmab: Consultancy, Other: Member of the Epcoritamab Global Council, Research Funding; Nurix: Research Funding; Viracta: Research Funding; ADC Therapeutics: Research Funding; Roche: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding; BMS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau. Sunkersett: AbbVie: Current Employment. Morehouse: Genmab: Current Employment, Current equity holder in publicly-traded company. Steele: Genmab: Current Employment, Other: owns Genmab stock; Janssen: Other: owns Janssen stock; AbbVie: Other: owns AbbVie stock. Marek: Genmab: Current Employment. Wang: Genmab: Current Employment. Hoehn: Genmab: Current Employment, Current equity holder in publicly-traded company. 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; Takeda: Honoraria, 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; 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. Belada: Swixx: Consultancy; Pharmacyclis: Research Funding; Astra Zenecca: Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Regeneron: Research Funding; Gilead Sciences: Consultancy; AbbVie: Consultancy; Swixx BioPharma: Consultancy.

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