DURABLE EFFICACY WITH FIXED-DURATION EPCORITAMAB + POLATUZUMAB, VEDOTIN, RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE (POLA-R-CHP) FOR 1L DLBCL (EPCORE NHL-5)

Abstract

Introduction: First-line (1L) standard of care for diffuse large B-cell lymphoma (DLBCL) is R plus C, H, vincristine, and P (R-CHOP), and it continues to evolve with pola-R-CHP showing higher complete response rates (CRR) of 78% and longer progression-free survival than R-CHOP (Tilly 2022), However, additional therapies are needed to further improve cure rates for 1L patients (pts). Epcoritamab (epcor) is a subcutaneous CD3×CD20 bispecific antibody approved globally as a monotherapy for 3L+ R/R DLBCL with demonstrated safety and efficacy in combination with 1L R-CHOP and pola-R-CHP (CRRs, 87% [Falchi 2024] and 89% [Lavie 2024], respectively). Here we report 16.1 months (mos) follow-up data from the epcor + pola-R-CHP cohort of the Phase 1b/2 EPCORE NHL-5 (NCT05283720) study.

Methods: Pts with newly diagnosed CD20+ DLBCL, ECOG PS 0–2, and IPI score 2–5 received 21-day (d) cycles (c) of epcor + pola-R-CHP for 6 c, then 2 c of epcor monotherapy. Two step-up dosing of epcor was used in c1, followed by QW dosing during c2-4 and Q3W during c5-8. Corticosteroids were given during c1 to further mitigate cytokine release syndrome (CRS) with epcor. G-CSF or pegylated G-CSF was administered 1–2 d after administration of H, C, and pola during c1–6. Key endpoints included investigator-assessed response rate (ORR/CRR), time to response (TTR/TTCR), and safety; exploratory endpoints included biomarkers and pharmacokinetics (PK).

Results: As of Oct 1, 2024, 37 pts received epcor + pola-R-CHP. Median age was 64 years and 51% were female; 34 had DLBCL NOS, 1 high-grade B-cell lymphoma, and 2 follicular lymphoma; 54% had GCB disease and 43% non-GCB; 19% had IPI2, 25% had bulky disease. Median follow-up was 16.1 mos (95% CI: 11.1, 16.6). Among 35 response-evaluable pts, ORR was 100% (97% CRR [Table]) with similar findings across subgroups. Median TTR and TTCR were 2.7 mos (range: 1.3–3.3) and 2.8 mos (range: 1.3–10.9), respectively. Tx-emergent AEs (TEAEs) are summarized (Table). Three (8%) pts discontinued epcor and 2 (5%) discontinued pola-R-CHP due to an AE. The most common G3/4 AEs were neutropenia (65%), anemia (19%), and leukopenia (11%). One pt had a fatal TEAE (urosepsis) not considered related to epcor. Low-grade CRS occurred in 51% of pts (35% G1, 16% G2, no G3+), with expected onset primarily after the first full dose of epcor (C1D15). All CRS events resolved, with median resolution time of 2 d (range: 1–6). No ICANS was observed. PK and biomarker data will be presented later.

Conclusions: Fixed-duration epcor + pola-R-CHP with follow-up of 16.1 mos in pts with newly diagnosed DLBCL continues to show high ORR and CRR across all subgroups with no new safety signals. Data continue to support that adding epcor to 1L SOC drives deep and durable responses. CRS was low-grade with predictable timing of onset. These data reaffirm prior findings, demonstrate the versatility of subcutaneous epcor, and support the potential of this promising combination for 1L DLBCL.

Research funding declaration: Epcoritamab is being developed in collaboration between AbbVie and Genmab who funded this study and participated in the design of the study, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication.

Encore Abstract: EHA 2025

Keywords: aggressive B-cell non-Hodgkin lymphoma; molecular targeted therapies; indolent non-Hodgkin lymphoma

Potential sources of conflict of interest:

D. Lavie

Honoraria: AbbVie, Medison, MSD, Novartis, Roche, Takeda.

D. A. Kerr

Consultant or advisory role: AbbVie, Bristol Myers Squibb, Genentech, Incyte

Other remuneration: Speaker's Bureau: BeiGene, Genentech; Research funding: AbbVie.

A. Avigdor

Consultant or advisory role: Board of Directors or Advisory Committee Member: AbbVie, Bristol Myers Squibb, Gilead, Novartis, Roche, Takeda

I. Avivi

Honoraria: AbbVie, MSD, Medison, Novartis, Takeda.

D. Belada

Consultant or advisory role: Dr. Reddy's Laboratories, Genmab, Gilead Sciences, Janssen-Cilag, MorphoSys, Roche, Takeda

Other remuneration: Research funding: Dr. Reddy's Laboratories, Genmab, Gilead Sciences, Janssen-Cilag, MorphoSys, Pharmacyclics, Takeda; Travel, accommodations, expenses: AbbVie, Gilead Sciences, Roche, Takeda

P. Abrisqueta

Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Genmab, Gilead, Incyte, Janssen, Regeneron, Roche.

Honoraria: AbbVie, AstraZeneca, BeiGene, Genmab, Gilead, Incyte, Janssen, Regeneron, Roche

K. Izutsu

Consultant or advisory role: AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Carna BioSciences, Chugai, Eisai, Kyowa Kirin, Mitsubishi Tanabe, MSD, Ninoh Shinyaku, Novartis, Ono Pharmaceutical, Symbio, Takeda, Yakult, Zenyaku

Honoraria: AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Lilly, Genmab, Janssen, Kyowa Kirin, Meiji Seika Pharma, MSD, Nihon Kayaku, Novartis, Ono Pharmaceutical, Otsuka, Pfizer, Symbio, Takeda

Other remuneration: Research funding: AbbVie, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Genmab, Gilead, Incyte, Janssen, Kyowa Kirin, Loxo Oncology, MSD, Novartis, Otsuka, Pfizer, Regeneron, Yakult.

C. Grande-Garcia

Consultant or advisory role: Advisory Boards: AbbVie

H. Goto

Honoraria: AbbVie, Bristol Myers Squibb, Novartis, Gilead, Chugai, Kyowa Kirin, Takeda, Meiji, MSD

Other remuneration: Research funding: Sanofi, Bristol Myers Squibb, Gilead, Kyowa Kirin, Symbio.

M. Seliem

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

S. R. Siddani

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

N. Joshi

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

B. Noorani

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

N. Dixit

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

S. Diness Vindelov

Employment or leadership position: Employee of Genmab and owns Genmab stock

P. Jafarinasabian

Employment or leadership position: Employee of AbbVie and owns AbbVie stock.

C. Thieblemont

Consultant or advisory role: AbbVie, BeiGene, Bristol Myers Squibb/Celgene, Janssen, Kite/Gilead, Novartis, Regeneron, Roche, Takeda.