EPCORITAMAB MONOTHERAPY DEMONSTRATES DEEP AND DURABLE RESPONSES AT 3-YEAR FOLLOW-UP IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA

Introduction: Epcoritamab (epcor), a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved for relapsed/refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior lines of therapy (3L+) based on EPCORE NHL-1 FL (NCT03625037; US/EU; Linton KM, et al. Lancet Haem 2024;11:E593–E605) and NHL-3 FL (NCT04542824; Japan) expansion cohorts (EXP) results. NHL-1 cycle (C) 1 optimization cohort (OPT) implemented a 3-step-up dosing (3-SUD) regimen to support outpatient utilization of epcor in FL. We report 3-y follow-up (FU) from EXP and updated OPT results for epcor monotherapy in patients (pts) with 3L+ FL.

Methods: Pts with CD20+ R/R FL grade[G] 1–3A and ≥ 2 prior lines of systemic treatment (tx) received SC epcor in 28-d Cs until disease progression or unacceptable toxicity. NHL-1 (N = 128) and NHL-3 (N = 21) EXP were pooled for diversity; OPT is reported separately. For EXP, the primary endpoint was efficacy; secondary endpoints were minimal residual disease (ClonoSeq®) negativity and safety. Due to the disproportionate impact of COVID-19 pandemic on pts from EXP, sensitivity analyses with conservative adjustment for COVID-19 deaths were conducted for efficacy. For OPT, the primary endpoint was incidence and severity of cytokine release syndrome (CRS); secondary endpoints were response rates and safety.

Results: As of Dec 2024, median FU was 35 mo and 15.5 mo and median duration of tx was 9.7 mo and 11.4 mo in EXP(N = 149) and OPT(N = 86), respectively. Across cohorts, pts were heavily pretreated (median 3 prior lines) and had high-risk R/R FL features. In the pooled EXP, overall response rate (ORR) was 84.6% and complete response rate (CRR) was 67.1% (Table).

With longer-term FU, safety from EXP was generally consistent with previous reports. In EXP, conducted during the COVID-19 pandemic peak, 34.9% of pts had G3–4 infections (18.1% COVID-19) and 7.4% had G5 events (5.4% COVID-19). 28% of pts discontinued (d/c) tx due to tx-emergent adverse events (TEAEs; 12.1% COVID-19). G3 or higher infections were reported in 14.3% of pts on ≥ 2y of tx (n = 35).

In OPT, updated ORR/CRR were 91.9%/73.3%; time-to-event endpoint data were still maturing, with most pts alive (93%).

With additional FU, safety from OPT remained unchanged from prior reports of only low-grade CRS (39.5% G1 and 9.3% G2) and no immune effector cell-associated neurotoxicity syndrome (ICANS). In OPT, conducted post COVID-19 pandemic peak, 20.9% of pts had G3–4 infections (7.0% COVID-19, all G3); 1 pt had G5 TEAE of viral respiratory tract infection. TEAEs leading to tx d/c occurred in 11% (1.2% COVID).

Conclusions: Epcor monotherapy demonstrated deep and durable responses and manageable safety with no new safety signals at 3y in a large and diversified 3L+ FL global population. OPT cohort results show response rates consistent with those in EXP and confirm the favorable safety profile of epcor, with reduced rates and severity of CRS/ICANS with 3-SUD regimen, and lower post-pandemic COVID-19 rates.

Research funding declaration: Study is sponsored by Genmab A/S and AbbVie.

Encore Abstract: EHA 2025

Keywords: indolent non-Hodgkin lymphoma

Potential sources of conflict of interest:

K. M. Linton

Consultant or advisory role: Beigene, Celgene

Educational grants: Celgene

Other remuneration: Research funding: Beigene, Celgene, Janssen, Step Pharma, Regeneron, MorhoSys, MSD, Nurix, AstraZeneca; Speakers bureau: Celgene

J. M. Vose

Consultant or advisory role: Adaptive, Genmab, Ono

Other remuneration: Research Funding: Epizyme, Genmab, Loxo

W. Jurczak

Consultant or advisory role: Beigene, Janssen Cilag, AstraZeneca, Regeneron, AbbVie, Lilly, Roche, Takeda

Other remuneration: Research funding: Beigene, Janssen Cilag, AstraZeneca, Regeneron, AbbVie, Lilly, Roche, Takeda, Merck, MSD

P. J. Lugtenburg

Consultant or advisory role: BMS, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron, Sandoz, Y-mAbs Therapeutics

Other remuneration: Research grants: Takeda, Servier;

E. Gyan

Consultant or advisory role: Pfizer, Roche, Abbvie, Takeda, BMS, Sanofi

Other remuneration: Research funding: Novartis, Sanofi

J. C. Chavez

Consultant or advisory role: Kite/Gilead, Novartis, Karyopharm, MorphoSys, BeiGene, AbbVie, ADC Therapeutics, BMS, Epizyme, Genentech, Bayer

Honoraria: Kite/Gilead, Novartis, Karyopharm, MorphoSys, BeiGene, AbbVie, ADC Therapeutics, BMS, Epizyme, Genentech, Bayer

Other remuneration: Research funding: AstraZeneca, Merck, and Adaptive

A. Sureda

Consultant or advisory role: Takeda, BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite, Mundipharma, Bluebird

Honoraria: Takeda, BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite

Educational grants: Takeda, BMS, Roche

Other remuneration: Research Funding: Takeda; Speakers Bureau: BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite

H. Tilly

Consultant or advisory role: Roche, BMS, Incyte

Other remuneration: Research Funding: Roche, Astra-Zeneca, BMS, Incyte, Beigene, Daiichi Sankyo, Lilly, Novartis, Pharmacyclics, ADC Therapeutics, Epizyme

R. Córdoba

Consultant or advisory role: Takeda, Genmab, BMS, Kite, Janssen, Incyte, Gilead, Roche, AstraZeneca, BeiGene, Lilly, AbbVie, Johnson & Johnson, Kyowa Kirin

Honoraria: Incyte, Gilead, Roche, AstraZeneca, BeiGene, Lilly, AbbVie, Johnson & Johnson

Educational grants: Incyte, Gilead, Roche, AstraZeneca, BeiGene, Lilly, AbbVie, Johnson & Johnson

Other remuneration: Speakers Bureau: Takeda, BMS, Kite, Janssen, Roche, AstraZeneca, AbbVie

D. J. Lewis

Consultant or advisory role: Janssen, Lilly, Roche, BeiGene, Kite

M. Hutchings

Consultant or advisory role: AbbVie, BMS, Genmab, Janssen, Roche, Takeda

Other remuneration: Research support (paid to Institution): BMS, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, Takeda

M. Roost Clausen

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

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

Educational grants: Pfizer, AbbVie, Janssen, AstraZeneca, Genmab, Roche

J. Sancho

Consultant or advisory role: AbbVie, BeiGene, BMS, Gilead/Kite, Incyte, Janssen, Lilly, Miltenyi Biomedicine, Novartis, Roche

Honoraria: AbbVie, BeiGene, BMS, Gilead/Kite, Incyte, Janssen, Lilly, Novartis, Roche

T. Cochrane

Other remuneration: Research funding: BeiGene; Speakers bureau: Janssen-Cilag

S. Leppä

Consultant or advisory role: AbbVie, BeiGene, Genmab, Gilead, Incyte, Novartis, Orion, Roche

Honoraria: Gilead, Incyte, Novartis

Other remuneration: Research Funding (Paid to Institution): Bayer, BMS, Genmab, Hutchmed, Novartis, Nordic Nanovector, Roche

M. E. D. Chamuleau

Consultant or advisory role: AbbVie, Novartis, Sanofi

Other remuneration: Research funding: BMS, Gilead, and Genmab

C. Thieblemont

Consultant or advisory role: Novartis,

Honoraria: ADC Therapeutics, AstraZeneca, Incyte, Sanofi, Amgen, Novartis, Cellectis

P. F. Caimi

Consultant or advisory role: BMS, Novartis, Genentech, Synthekine, Luminary Therapeutics, ADC Therapeutics

Honoraria: Recordati, Abbvie, Sobi, Arvinas

Other remuneration: Research funding: Recordati, Abcon, Abbvie, BMS, Genentech, Synthekine, Luminary Therapeutics, Genmab, ADC Therapeutics, Profound Bio, Arvinas

Y. H. Karimi

Consultant or advisory role: AbbVie, ADC Therapeutics

Educational grants: Roche/Genentech

Other remuneration: Research funding: AbbVie, AstraZeneca, Lilly/Loxo, Merck, Roche/Genentech, Xencor

C. Andreadis

Consultant or advisory role: Abbvie, AstraZeneca, BMS, Genmab, Gilead, Roche, Seattle Genetics

K. Izutsu

Consultant or advisory role: AbbVie, AstraZeneca, Bayer, Beigene, BMS, Chugai, Daiichi Sankyo, Genmab, Gilead, Incyte, Janssen, Kyowa Kirin, LOXO Oncology, MSD, Novartis, Otsuka, Pfizer, Regeneron, Yakult

Honoraria: AbbVie, AstraZeneca, Bayer, Beigene, BMS, Chugai, Daiichi Sankyo, Genmab, Gilead, Incyte, Janssen, Kyowa Kirin, LOXO Oncology, MSD, Novartis, Otsuka, Pfizer, Regeneron, Yakult

Other remuneration: Research funding: AbbVie, AstraZeneca, Bayer, Beigene, BMS, Chugai, Daiichi Sankyo, Genmab, Gilead, Incyte, Janssen, Kyowa Kirin, LOXO Oncology, MSD, Novartis, Otsuka, Pfizer, Regeneron, Symbio, Yakult

N. Fukuhara

Other remuneration: Speakers bureau: Abbvie, AstraZeneca, BMS, Chugai, CSL Behring, Eisai, Eli Lilly, Genmab, Gilead, Janssen, Kyowa Kirin, Nippon Shinyaku, Novartis, Ono, Sanofi, Solasia, Symbio, Takeda; Research funding: Abbvie, Chugai pharma, Chordia therapeutics, Genmab, Haihe pharma, Incyte, Ono pharma

E. Favaro

Employment or leadership position: Genmab

Stock ownership: Genmab

P. Patah

Employment or leadership position: AbbVie

Stock ownership: AbbVie

M. Geybels

Employment or leadership position: Genmab

Stock ownership: Genmab

I. Altintaş

Employment or leadership position: Genmab

Stock ownership: Genmab

C. Morehouse

Employment or leadership position: Genmab

Stock ownership: Genmab

U. Vitolo

Consultant or advisory role: AbbVie, Genmab, Gilead, Incyte, Regeneron

Other remuneration: Lecture fees: AbbVie, AstraZeneca, Gilead, Incyte, MSD, Regeneron, Roche