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3106 Fixed-Duration Epcoritamab + R-Mini-CHOP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma Ineligible for Full-Dose R-CHOP: Updated Results from Arm 8 of the Epcore NHL-2 Trial

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Combination therapy, 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
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Lori A. Leslie, MD1*, Chan Y. Cheah, MBBS, DMSc2*, Franck Morschhauser, MD, PhD3, Justin M. Darrah, MD4*, Joshua Brody, MD5*, David Belada, MD, PhD6, Juraj Duras, MD7*, Joost S.P. Vermaat8, Gerardo Musuraca, MD, PhD9*, Kojo Osei-Bonsu, MD10*, Yi Hao, DrPH11*, Kimberly G. Archer11*, Monica Wielgos-Bonvallet, PhD11*, Ali Rana, MD, PhD11* and Yasmin H. Karimi, MD12

1John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ
2Sir Charles Gairdner Hospital and the University of Western Australia, Nedlands, Australia
3University of Lille, CHU Lille, Lille, France
4Division of Hematology and Cellular Therapy, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
5Icahn School of Medicine at Mount Sinai, New York, NY
64th Department of Internal Medicine – Hematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic
7Department of Hemato-Oncology, University Hospital and Faculty of Medicine, Ostrava, Czech Republic
8Leiden University Medical Center, Leiden, Netherlands
9Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori", Meldola, Italy
10AbbVie, North Chicago, IL
11Genmab, Plainsboro, NJ
12Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI

Introduction: A standard treatment for patients (pts) with previously untreated (1L) diffuse large B-cell lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, certain pts are ineligible to receive full-dose R-CHOP due to advanced age, frailty, or underlying comorbidities. Dose-attenuated R-CHOP (R-mini-CHOP) has become a standard first-line regimen for these pts despite suboptimal outcomes, including overall response rates (ORRs) and complete response (CR) rates of approximately 70% and 40%–60%, respectively, and a 2-y progression-free survival (PFS) rate of only 47%. Epcoritamab, a CD3xCD20 bispecific antibody, in combination with R-mini-CHOP demonstrated encouraging efficacy (ORR, 100%) and a manageable safety profile in pts with 1L DLBCL who were ineligible for full-dose R‑CHOP (Vermaat et al, ASH 2023; median follow-up, 9.4 mo). Here, we report updated results with longer follow-up from arm 8 of the EPCORE® NHL-2 trial (phase 1b/2; NCT04663347) evaluating epcoritamab + R-mini-CHOP in this population.

Methods: Adult pts with 1L CD20+ DLBCL who were ineligible for full-dose R-CHOP due to age ≥75 y or age ≥65 y with comorbidities (reduced left ventricular ejection fraction, history of myocardial infarction [>6 mo prior to enrollment], exertional chest pain, arrhythmia [grade ≤2], hypertension requiring treatment, or diabetes) were enrolled. Pts received fixed-duration subcutaneous epcoritamab (QW, cycles [Cs] 1–2 [21 d each]; Q3W, C3–6 [21 d each]; Q4W, C7–8 [28 d each]; with step-up dosing in C1 [0.16 mg on C1D1 and 0.8 mg on C1D8]) + R-mini-CHOP (Q3W, C1–6). The primary endpoint for this population was ORR as determined by PET-CT and Lugano criteria. Minimal residual disease (MRD) negativity was assessed as a secondary endpoint using the exploratory AVENIO ctDNA method.

Results: As of May 15, 2024, 28 pts were treated with epcoritamab 48 mg + R-mini-CHOP. The median age was 81 y (range, 74–90), 19 pts (68%) had IPI 3–5, 15 pts (54%) had stage IV disease, and 11 pts (39%) had bulky disease (≥7 cm); 13 pts (46%) had germinal center B-cell (GCB)–type disease, 11 pts (39%) had non-GCB type, and 4 pts (14%) had unknown type. The median follow-up was 16.8 mo (range, 2.5+ to 23.1), with 22 pts (79%) having completed treatment per protocol and none remaining on treatment. Median relative dose intensity of R-mini-CHOP was ≥94%. ORR was 89% (25/28), with CR in 82% of pts (23/28). An estimated 92% of responders remained in response at 12 mo, and an estimated 91% of complete responders remained in CR at 12 mo. The estimated 12-mo PFS and overall survival rates were 88% and 96%, respectively. Of 21 MRD-evaluable pts, 20 (95%) were MRD negative using the AVENIO ctDNA method and a cutoff of <1 mutant molecule per mL. The most common treatment-emergent AEs (TEAEs) of any grade (occurring in ≥25% of pts) were CRS (54%), neutropenia (43%), constipation (29%), fatigue (29%), anemia (25%), fall (25%), and pneumonia (25%). All CRS events were low grade (25% grade 1, 29% grade 2), and most events were observed after the first full dose of epcoritamab. All CRS events resolved, and 1 pt (4%) discontinued epcoritamab due to CRS. No ICANS or clinical tumor lysis syndrome events were reported. Overall, 3 pts (11%) discontinued epcoritamab due to TEAEs, including 1 pt (4%) who had grade 5 TEAEs (confusional state not related to treatment and cytomegalovirus infection reactivation considered related to treatment in a pt aged 90 y also diagnosed with acute cerebrovascular accident).

Conclusions: Epcoritamab + R-mini-CHOP treatment continues to demonstrate encouraging and durable efficacy in pts with 1L DLBCL who were not candidates for full-dose R-CHOP, including elderly and high-risk pts. These results are promising compared with historical outcomes with R-mini-CHOP. The safety profile was manageable, with no new safety signals, no ICANS, and only low-grade CRS events. These results support further clinical evaluation of fixed-duration epcoritamab in combination with chemotherapy in early lines of therapy, including in pts with high-risk features.

Disclosures: Leslie: Seagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lily: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy, Speakers Bureau; Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche/Genenetech: Consultancy, Speakers Bureau; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Evolveimmune: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy; Karyopharm: Consultancy. Cheah: BMS, Roche, AbbVie: Research Funding; Roche: Other: Travel Expenses; Roche, Janssen, MSD, Gilead, Ascentage Pharma, AstraZeneca, Lilly, TG Therapeutics, BeiGene, Novartis, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Morschhauser: Epizyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Honoraria; Roche/Genentech: Consultancy, Honoraria, Other: Payment for Expert Testimony, Honoraria for Scientific Lectures; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Servier: Consultancy. Darrah: Kite, MorphoSys: Membership on an entity's Board of Directors or advisory committees. Belada: Regeneron: Research Funding; AbbVie: Consultancy; Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swixx BioPharma: Consultancy; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy; Eli Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; Astra Zenecca: Research Funding; Gilead Sciences: Consultancy; Takeda: Consultancy, Research Funding; Pharmacyclis: Research Funding; Swixx: Consultancy. Duras: Roche, Takeda, BMS, Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vermaat: Secura Bio: Consultancy. Musuraca: AbbVie, Incyte, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees. Osei-Bonsu: AbbVie: Current Employment. Hao: Genmab: Current Employment. Archer: Genmab: Current Employment. Wielgos-Bonvallet: Genmab: Current Employment, Current equity holder in publicly-traded company. Rana: Genmab: Current Employment. Karimi: Lilly/Loxo: Research Funding; Roche/Genentech: Other: Travel Expenses, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Xencor: Research Funding; AstraZeneca: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Merck: Research Funding.

*signifies non-member of ASH