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609 Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma:Phase 1/2 Trial Update

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological IV
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell lymphoma, Diseases, indolent lymphoma, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022: 5:00 PM

Lorenzo Falchi, MD1, Pau Abrisqueta, MD, PhD2*, Marcel Nijland, MD, PhD3*, Sirpa Leppä, MD, PhD4, Martin Hutchings, MD, PhD5*, Harald Holte, MD, PhD6,7, Reid W. Merryman, MD8, Pieternella Lugtenburg, MD, PhD9, Sven de Vos, MD, PhD10, Chan Y. Cheah, MBBS, FRACP, FRCPA, DMSc11, Jacob Haaber Christensen, MD, PhD12*, Luca Arcaini13,14*, Kristina Drott, MD, PhD15*, Mats Hellström, MD, PhD16*, Lori A. Leslie, MD17*, Umberto Vitolo, MD18, Ali Rana, MD, PhD19*, Aqeel Abbas, MS19*, Liwei Wang, PhD19*, Minh Dinh, MD20* and David Belada, MD, PhD21*

1Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY
2Hospital Universitari Vall d’Hebron, Barcelona, Spain
3Department of Hematology, University Medical Center Groningen and University of Groningen, Groningen, Netherlands
4Helsinki University Hospital Cancer Center, Helsinki, Finland
5Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark
6Oslo University Hospital, Oslo, Norway
7KG. Jebsen Centre for B cell Malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway, Oslo, Norway
8Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
9Department of Hematology, On behalf of the HOVON lymphoma working group, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, Netherlands
10Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA
11Sir Charles Gairdner Hospital, Nedlands, Australia
12Odense University Hospital, Odense, Denmark
13Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
14Department of Molecular Medicine, University of Pavia, Pavia, Italy
15Skåne University Hospital, Lund, Sweden
16Uppsala University Hospital, Uppsala, Sweden
17Hackensack University Medical Center, Hackensack, NJ
18Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
19Genmab, Princeton, NJ
20AbbVie, Inc., North Chicago, IL
214th Department of Internal Medicine – Hematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic

Background: For patients with relapsed or refractory (R/R) follicular lymphoma (FL), therapies such as rituximab + lenalidomide (R2) have demonstrated efficacy and acceptable safety. However, better treatments are needed to help more patients achieve deeper and more durable responses. Epcoritamab is a subcutaneously administered bispecific antibody that simultaneously binds to CD3 on T cells and CD20 on B cells to kill malignant B cells. R2 and epcoritamab have nonoverlapping toxicity profiles and, therefore, may be safely combined. In addition, the immunomodulatory properties of lenalidomide may enhance the therapeutic potential of epcoritamab. Preliminary results from arm 2b of the phase 1/2 EPCORE NHL-2 trial (NCT04663347), which tested R2 and epcoritamab in patients with R/R FL, showed an overall response rate of 93% and a complete metabolic response rate of 61% at the first assessment (6 wk; Falchi et al, ASCO 2022). Here we present updated data on a larger cohort and longer follow-up from arm 2b of EPCORE NHL-2.

Methods: Adults with R/R CD20+ FL were treated with subcutaneous epcoritamab 48 mg + standard R2 for 12 cycles of 28 d each. Epcoritamab was dosed as follows: QW, cycles 1 and 2; Q4W, cycles ≥3 up to 2 y. Step-up epcoritamab dosing and corticosteroid prophylaxis were required during cycle 1 to mitigate CRS. PET-CT was used to assess responses per Lugano 2014 criteria.

Results: As of the data cutoff date of June 10, 2022, 62 patients had received epcoritamab (48 mg) + R2. The median age was 65 y (range, 30–79), 58% of patients had stage IV disease, 52% had FLIPI 3–5, 31% had primary refractory disease, and 47% had experienced disease progression within 24 mo after starting first-line treatment. Half of patients (50%) had received 1 prior line of therapy (range, 1–9). Treatment was ongoing in 56 patients (90%), with a median follow-up of 4.0 mo. Six patients discontinued therapy due to disease progression (n=4) or other reasons (death due to COVID-19, n=1; reason unknown, n=1). The most common treatment-emergent AEs of any grade were CRS (37%; 27% grade 1, 10% grade 2, no grade 3–4), neutropenia (29%; 5% grade 1–2, 24% grade 3–4), fatigue (26%; 24% grade 1–2, 2% grade 3–4), and injection-site reactions (26%; all grade 1–2). Most CRS events (in 35% of all evaluable patients) occurred after the first full dose of epcoritamab. All CRS events resolved (median time to resolution, 2 d; range, 1–4), no patients discontinued treatment due to CRS, and 5 patients received tocilizumab. ICANS (grade 1) occurred in 1 patient 22 d from the start of treatment, and it resolved in 7 d. There were no clinical tumor lysis syndrome events. Among 41 efficacy-evaluable patients, the overall response rate was 95% (39/41), with 73% of patients (30/41) achieving a complete metabolic response (CMR) as their best overall response. Most CMRs (27/30) were achieved by the first assessment (6 wk), and nearly all (29/30) were ongoing at the time of data cutoff. Of the 9 patients with a partial metabolic response, 6 had an ongoing response at the time of data cutoff. The longest duration of response was 4.5+ mo. Median progression-free survival was not reached (Figure).

Conclusions: In patients with R/R FL, subcutaneous epcoritamab + R2 demonstrated a manageable safety profile with only low-grade CRS events, mostly observed following the first full dose and all of which resolved. No new safety signals were detected. Data from this cohort are very encouraging with a high CMR rate observed in patients with R/R FL. These data are consistent with prior results from the EPCORE NHL-2 trial and supportive of ongoing investigation of epcoritamab + R2 in patients with R/R FL. A phase 3 trial of epcoritamab + R2 compared with R2 alone in patients with R/R FL (EPCORE FL‑1) will open in 2022.

Disclosures: Falchi: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, 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; Seagen: Membership on an entity's Board of Directors or advisory committees. Abrisqueta: Sandoz: Honoraria; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy. Nijland: Genmab: Consultancy; Takeda: Research Funding; Roche: Research Funding. Leppä: Nordic Nanovector: Research Funding; Genmab: Research Funding; Beigene: Consultancy; Pfizer: Consultancy; Orion Pharma: Consultancy; Bayer: Research Funding; BMS: Consultancy, Research Funding; Gilead Sciences: Consultancy, Honoraria; Roche: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria. Hutchings: Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Incyte: Research Funding; Genmab: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; AbbVie: Consultancy; Janssen: Consultancy, Research Funding; Novartis: Research Funding; Genentech: Research Funding; Celgene, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, Takeda: Research Funding; AbbVie, Celgene, Genmab, Janssen, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees. Holte: Gilead: Honoraria, Other: Advisory board; Nordic Nanovector: Honoraria, Other: Safety committee; Takeda: Honoraria, Other: Advisory board; Incyte: Honoraria, Other: Advisory board; Genmab: Honoraria, Other: Safety committee; Novartis: Honoraria, Other: Advisory board. Merryman: Genentech/Roche: Research Funding; Merck & Co., Kenilworth, NJ: Research Funding; Epizyme: Consultancy; Intellia: Consultancy; Abbvie: Consultancy; Bristol Myers Squib: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Genmab: Consultancy, Research Funding; Pfizer: Research Funding. Lugtenburg: Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, 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; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. de Vos: BeiGene: Other: Participation on a Data Safety Advisory Board. Cheah: Novartis: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Ascentage Pharma: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel expenses, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Arcaini: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees. Drott: Respiratorius AB: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Honoraria; Roche: Honoraria. Leslie: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celegene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Jansssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Karyopharm: Speakers Bureau; Eli Lily: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Vitolo: Gilead, Incyte, Genmab, Bayer, Constellation, Seattle-Genetics: Membership on an entity's Board of Directors or advisory committees; Abbvie, Incyte, Janssen, Servier: Speakers Bureau. Rana: Genmab: Current Employment. Abbas: Genmab: Current Employment. Wang: Genmab: Current Employment. Dinh: AbbVie: Current Employment, Current equity holder in publicly-traded company. Belada: Genmab: Research Funding.

*signifies non-member of ASH