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3569 Phase 3 Trial (EPCORE DLBCL-1) of Epcoritamab Versus Standard of Care in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Clinical Trials, Biological, Lymphomas, Non-Hodgkin Lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell Lymphoma, Diseases, Aggressive Lymphoma, Therapies, Lymphoid Malignancies
Monday, December 13, 2021, 6:00 PM-8:00 PM

Christopher P. Fox, MBChB(Hons), MRCP, FRCPath, PhD1*, Michael Roost Clausen, MD, PhD2*, Pieternella Lugtenburg, MD, PhD3, Anna Sureda4, Pier Luigi Zinzani, MD5, Jun Wu, MD6*, Laura Finn, MD7, Signe Diness Vindeløv, MD, PhD8* and Catherine Thieblemont, MD, PhD9

1Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
2Vejle Hospital, Vejle, Denmark
3Department of Hematology, On behalf of the HOVON lymphoma working group, Erasmus MC Cancer Institute, Rotterdam, Netherlands
4Institut Català d'Oncologia-Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain
5Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of Hematology “L. e A. Seràgnoli,” University of Bologna, Bologna, Italy
6AbbVie, North Chicago, IL
7Ochsner Medical Center, New Orleans, LA
8Genmab A/S, Copenhagen, Denmark
9Assistance Publique & Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Hémato-oncologie, Université de Paris, Paris, France

Background: Patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are refractory to or have relapsed (R/R) after treatment with chemotherapy and an anti-CD20 monoclonal antibody (mAb) have a poor prognosis. New treatment options are needed to improve outcomes. Epcoritamab, a novel, subcutaneously (SC) administered bispecific antibody, binds to CD3 on T lymphocytes and CD20 on B-cell non-Hodgkin lymphoma (NHL) cells to induce potent and selective killing of malignant CD20+ B cells. In an ongoing phase 1/2 dose-escalation trial in heavily pretreated pts with B-cell NHL (N=68), epcoritamab showed a tolerable safety profile and substantial single-agent antitumor activity, with a complete response (CR) rate of 38% and an overall response rate (ORR) of 88% in pts with R/R DLBCL (at 48-mg dose, n=8; EPCORE NHL-1 [NCT03625037]). Furthermore, all 4 evaluable pts with R/R DLBCL previously treated with chimeric antigen receptor T-cell (CAR-T) therapy achieved objective responses and 2 achieved CRs. These encouraging data support the potential for epcoritamab to improve clinical outcomes in pts with R/R DLBCL. Herein we describe the ongoing phase 3 trial of epcoritamab vs standard of care (SOC) treatment in pts with R/R DLBCL.

Study Design and Methods: EPCORE DLBCL-1 is a global, randomized, open-label, multicenter phase 3 trial designed to evaluate the efficacy of epcoritamab vs investigator’s choice of SOC with rituximab, gemcitabine, and oxaliplatin (R-GemOx) or bendamustine and rituximab (BR) in adults with R/R disease of one of the following CD20+ aggressive B-cell NHL histologies: (a) DLBCL, not otherwise specified, including de novo DLBCL or DLBCL histologically transformed from follicular lymphoma (FL); (b) “double- or triple-hit” DLBCL (high-grade B-cell lymphoma, with MYC and B-cell lymphoma [BCL] 2 and/or BCL6 translocations), including de novo “double- or triple-hit” DLBCL or “double- or triple-hit” DLBCL histologically transformed from FL; or (c) FL grade 3B. Other key eligibility criteria include: ≥1 line of prior chemotherapy that included treatment with an anti-CD20 mAb, Eastern Cooperative Oncology Group performance status 0–2, and prior failure of/ineligibility for autologous stem cell transplantation. Prior CAR-T therapy is allowed. Approximately 480 pts will be randomized 1:1 to receive either SC epcoritamab or intravenous R-GemOx (every 2 weeks, maximum of four 28-day cycles: 8 doses) or intravenous BR (every 3 weeks, maximum of six 21-day cycles; 12 doses of bendamustine, 6 doses of rituximab). Epcoritamab will be administered at the recommended phase 2 dose from the EPCORE NHL-1 trial in 28-day cycles (cycles 1–3: once weekly; cycles 4–9: every 2 weeks; cycle ≥10: every 4 weeks) until disease progression or unacceptable toxicity. The primary end point is overall survival. Key secondary end points include progression-free survival, ORR, duration of response, time to response, and safety. The study is currently enrolling in Australia, Austria, Belgium, Denmark, Finland, France, Hungary, Japan, the Netherlands, Norway, Poland, Republic of Korea, Singapore, Spain, Sweden, the United Kingdom, and the United States, and it will open for enrollment in additional countries (NCT04628494).

Disclosures: Fox: Roche: Honoraria, Research Funding; Genmab: Honoraria; Celgene/BMS: Honoraria; Abbvie: Honoraria, Research Funding; Morphosys: Honoraria; Incyte: Honoraria; Atarabio: Honoraria; Astrazeneca: Honoraria; Takeda: Honoraria, Research Funding; Gilead: Honoraria, Research Funding. Clausen: Gilead: Consultancy, Other: Travel expences 15th ICML ; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lugtenburg: Roche: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Genmab: Honoraria; Regeneron: Honoraria; Incyte: Honoraria; Celgene: Honoraria, Other: Non-financial support; Travel support. Sureda: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Novartis: 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; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy. Zinzani: Sanofi: Consultancy, 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, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Wu: AbbVie: Current Employment. Finn: Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; BeiGene: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy, Speakers Bureau. Vindeløv: Genmab: Current Employment. Thieblemont: Hospira: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bayer: Honoraria; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses .

*signifies non-member of ASH