Lorenzo Falchi MD; ASH 2025: Bispecific Antibody Epcoritamab Combination Beats Standard of Care for Patients with Relapsed/Refractory Follicular Lymphoma

Bispecific Antibody Epcoritamab Combination Beats Standard of Care for Patients with Relapsed/Refractory Follicular Lymphoma

An interview with:

Lorenzo Falchi MD, Lymphoma Service, Attending Physician, Memorial Sloan Kettering Cancer Center, New York NY, USA

ORLANDO, USA—A bispecific antibody to treat follicular lymphoma has outperformed standard rituximab plus lenalidomide in patients whose disease has relapsed or who are refractory to standard first-line treatments.  This was in the phase three epcore FL-1 trial in which patients receiving rituximab and lenalidomide were randomly assigned to have the CD3xCD20 bispecific Epcoritamab or a placebo added to their therapy.

At the 2025 Annual Meeting of the American Society of Hematology the findings were reported by Lorenzo Falchi MD, Lymphoma Service, Attending Physician, Memorial Sloan Kettering Cancer Center, New York NY, USA, who afterwards spoke with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Lorenzo Falchi MD

IN: [GOODWIN] “ I’m at the American …..

OUT:    ……..of Oncology, I’m Peter Goodwin  7:58

ASH 2025 ABSTRACT TITLE:

“primary Phase 3 results from the epcore FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma”

https://ashpublications.org/blood/article/146/Supplement%201/466/554305/primary-Phase-3-results-from-the-epcore-FL-1-trial

Blood (2025) 146 (Supplement 1): 466.

https://doi.org/10.1182/blood-2025-466

AUTHORS

Lorenzo Falchi1, Marcel Nijland2, Huiqiang Huang3, Kim Linton4, John Seymour5, Rong Tao6, Michal Kwiatek7, Abel Costa8, Theodoros Vassilakopoulos9, Richard Greil10, Ana Jiménez Ubieto 11, ShaneGangatharan12, Ohad Benjamini13, Catherine Thieblemont14, Alessandra Tucci15, Anna ElinderCamburn16, Arpad Illes17, Jan Novak18, Miguel Pavlovsky19, Andrew McDonald20, Dok Hyun Yoon21, Yuko Mishima22, Gauri Sunkersett23, Jian Mei23, Nabanita Mukherjee23, Feng Zhu23, Elena Favaro24, Franck Morschhauser25

INSTITUTIONS:

1 Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, United States,

2 University Medical Center Groningen, University of Groningen, Groningen, Netherlands,

3 Sun Yat-sen University, Guangzhou, China,

4 The Christie NHS Foundation Trust, Manchester Cancer Research Centre, and Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom,

5 Peter MacCallumCancer Centre and The Royal Melbourne Hospital, Melbourne, Australia,

6 Fudan University Cancer Hospital, Shanghai, China,

7 Aidport Clinical Trials Hospital, Skorzewo, Poland,

8Instituto D’Or de Pesquisa e Ensino, São Paulo, Brazil,

9 Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece,

10 Paracelsus Medical University Salzburg; Salzburg Cancer Research InstituteCenter for Clinical Cancer and Immunology Trials; Cancer Cluster Salzburg, Salzburg, Austria,

11 Hospital Universitario 12 de Octubre, Madrid, Spain,

12 Fiona Stanley Hospital, Murdoch, Australia,

13 The Chaim Sheba Medical Center, Ramat Gan, Israel,

14 Hôpital Saint-Louis, Paris, France,

15 ASST degli Spedali Civili di Brescia, Brescia, Italy,

16 North Shore Hospital, Auckland, New Zealand,

17 Debreceni Egyetem-Klinikai Kozpont, Debrecen, Hungary,

18 Fakultni nemocnice Kralovske Vinohrady, Prague, Czech Republic,

19 FUNDALEU, Buenos Aires, Argentina,

20 Alberts Cellular Therapy, Gauteng, South Africa,

21 Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea, Rep. of South,

22 Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan,

23 AbbVie Inc., North Chicago, IL, United States,

24 Genmab, Copenhagen, Denmark,

25 Hôpital Claude Huriez, Lille, France

INTRODUCTION:

Patients (pts) with relapsed/refractory (R/R) follicular lymphoma FL have limited second line (2L) treatment options, rituximab and lenalidomideR2being the only 2L alternative to immunochemotherapy-based therapy. Epcoritamab (epcor), a CD3xCD20 bispecific antibody, is approved for R/R FL as monotherapy after ≥2 lines of systemic therapy. Epcor plus R2 (E+R2) is a chemotherapy-free regimen which showed promising antitumor activity (97% overall response rate [ORR], 87% complete response [CR] rate) and manageable safety in the phase 1b/2 EPCORE NHL-2 trial (Falchi et al, ASH 2024). We report the results of EPCORE FL-1: the first global phase 3 trial of fixed-duration bispecific antibody regimen E+R2 vs R2 in pts with 2L+ FL (NCT05409066).

METHODS:

Adults with CD20+ FL R/R after at least 1 prior line, who met GELF criteria, were randomized to receive E+R2or R2for up to 12 cycles (C). Subcutaneous epcor was administered using a 2-step-up dose (2SUD) or 3-step-up dose (3SUD) regimen and full doses (48mg) thereafter. Epcor was administered weekly in C1–3 and q28 days from C4–12. Intravenous rituximab was administered weekly in C1 and q28 days during C2–5. Oral lenalidomide was administered daily from day 1–21 during C1–12. Pts received mandatory CRS prophylaxis in C1. Dual primary endpoints were ORR and progression-free survival (PFS) assessed by independent review committee per Lugano criteria. Secondary endpoints included CR rate (CRR), overall survival (OS), duration of response/CR (DOR/DOCR), and safety.

RESULTS:

As of the Jan 10, 2025 data cut-off, 488 pts were randomized to receive E+R2 (N=243) or R2alone (N=245). Pt characteristics were generally well balanced across the two arms. Pts treated with E+R2 vs R2had a median age of 60 years (range, 30–84) vs 63 years (range, 24–89), Ann Arbor stage III-IV in 84.8% vs 81.6%, double refractory disease in 35.4% vs 35.9%, and POD24 in 43% vs 36%, respectively. The median number of prior lines of treatment was 1 (range, 1–7) vs 1 (range, 1–6), respectively. The median duration of follow-up was 10.4 months (95% CI: 9.8, 11.1). A preplanned interim analysis was conducted after the first 232 pts achieved 12 months of follow-up post-randomization, and the ORR was significantly improved in pts treated with E+R2 (95.7% [95% CI: 90.2, 98.6]) vs R2(81.0% [95% CI: 72.7, 87.7]; P<.0001). The 12-month DOR was 91.4% (95% CI: 84.0, 95.4) vs 57.0% (95% CI: 44.2, 68.0), respectively. In the full ITT population (N=488), PFS was significantly longer in pts treated with E+R2 vs those treated with R2 (hazard ratio [HR] 0.21; 95% CI: 0.13, 0.33; P<.0001). Additionally, E+R2 led to a significant improvement in CRR vs R2 (74.5% [95% CI: 68.5, 79.8] vs 43.3% [95% CI: 37.0, 49.7]; P<.0001). Similar improvements in response rates were observed in all pre-definedhigh-risksubgroups (eg, primary/double refractory disease, POD24). Among 131 pts receiving 3SUD in the E+R2arm, CRS events were low grade (G) and occurred in 24.4% of pts (G1, 19.1%; G2, 5.3%); most occurred at time of first 48mg full epcor dose and all resolved. One event of ICANS (G1) was reported in the E+R2 arm and resolved. G3/4 TEAEs were reported in 88.1% of pts receiving E+R2vs 62.2% with R2, the difference being primarily driven by higher rates of G3/4 neutropenia (66.3% vs 37.8%) and G3/4 infections (29.2% vs 13.4%). Rates of G3/4 febrile neutropenia were 6.2% (E+R2) vs 2.1% (R2). Fatal TEAEs occurred in 0.8% (n=2) vs 2.9% (n=7) with E+R2 vs R2, respectively; with no fatal events deemed related to epcor. TEAEs leading to discontinuation occurred in 16.0% of cases for E+R2 vs 11.8% for R2. Updated data from prespecified second interim analysis on all efficacy endpoints will be available at the time of presentation.

CONCLUSION:

Epcor is the first CD20xCD3 bispecific antibody to demonstrate clinical benefit over standard of care in a randomized phase 3 trial in patients with FL, with statistically significant improvements in ORR, CR rate, and a 79% reduction in the risk of progression or death. Higher rates of G3/4 neutropenia and infections were observed in E+R2, but these were manageable and none were fatal. CRS was low grade and the timing was predictable. E+R² sets a new benchmark as a readily available treatment, is suitable for outpatient administration, and has the potential to become a new standard of care in 2L+ FL.

260130 Audio Journal of Oncology ASH 2025