Epcoritamab Combination Receives FDA Approval for Relapsed, Refractory Follicular Lymphoma

Epcoritamab-bysp (Epkinly; Genmab, AbbVie) in combination with lenalidomide (Revlimid; Bristol Myers Squibb) and rituximab (Rituxan, Genentech and Biogen; FCR) received FDA approval for patients with relapsed or refractory follicular lymphoma (RRFL). The decision was supported by data from the EPCORE FL-1 trial (study M20-638; NCT05409066).¹

Epcoritamab-bysp is a bispecific T-cell engager (BiTE) designed to link CD3 on healthy T cells with CD20 on malignant B cells, triggering targeted apoptosis. In 2024, it became the first and only FDA-approved BiTE therapy indicated for patients with RRFL after 2 or more lines of therapy based on data from the phase 1/2 EPCORE NHL-1 study (NCT03625037). In the trial, epcoritamab-bysp yielded a high overall response rate (ORR) of 82% and a complete response (CR) of 63%.^2-4

Epcoritamab-bysp’s clinical benefit continued in the randomized, open-label EPCORE FL-1 trial. The trial involved 488 patients with RR FL who were randomized 1:1 to receive epcoritamab-bysp plus lenalidomide and rituximab or lenalidomide and rituximab alone for 12 cycles (28 days). The population had a median of 1 prior line of systemic therapy (range: 1-7) of whom 24% and 17% had 2 and 3 or more prior lines, respectively.⁵

The primary end points of the trial were ORR and progression-free survival (PFS) as assessed by an independent review committee (IRC) using Lugano 2014 Criteria. Key secondary end points included overall survival and complete response.^1,5

Treatment with epcoritamab-bysp led to statistically meaningful outcomes in ORR and PFS. The PFS hazard ratio was 0.21 (95% CI: 0.13–0.33; P < .0001). Median PFS was not reached in the epcoritamab-bysp arm (95% CI: 21.9 months–NR), compared with 11.2 months (95% CI: 10.5–NR) in the lenalidomide and rituximab arm. The ORR was 89% (95% CI: 84–93) with epcoritamab-bysp versus 74% (95% CI: 68–79) in the lenalidomide and rituximab group.⁵

Regarding safety, serious adverse reactions occurred in 51% of the patients in the epcoritamab-bysp arm, including serious infections in 28%. Cytokine release syndrome (CRS) occurred in 24% of patients, including serious CRS in 12%. Immune effector cell-associated neurotoxicity syndrome occurred in 0.8%.⁵

The recommended regimen for epcoritamab-bysp plus lenalidomide and rituximab includes subcutaneous epcoritamab-bysp given over 12 28-day cycles, along with lenalidomide on days 1 through 21 of each cycle and rituximab during the first 5 cycles.⁵

Epcoritamab-bysp is initiated with a 3-step dose escalation in cycle 1 (0.16 mg on day 1, 0.8 mg on day 8, 3 mg on day 15, and 48 mg on day 22). This is followed by weekly 48 mg doses during cycles 2 and 3, then 48 mg doses every 4 weeks from cycles 4 through 12.⁵

REFERENCES

1. Study of subcutaneous epcoritamab in combination with intravenous rituximab and oral lenalidomide (R2) to assess adverse events and change in disease activity in adult participants with follicular lymphoma (EPCORE FL-1). Clinicaltrials.gov. Updated July 28, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT05409066

2. Gerlach A. Epcoritamab-bysp yields long-term disease remission in patients with relapsed, refractory large B-cell lymphoma. Pharmacy Times. May 29, 2025. Accessed November 18, 2025. https://www.pharmacytimes.com/view/epcoritamab-bysp-yields-long-term-disease-remission-in-patients-with-relapsed-refractory-large-b-cell-lymphoma

3. Gallagher A. FDA approves epcoritamab for treatment of relapsed, refractory follicular lymphoma. Pharmacy Times. June 27, 2025. Accessed November 18, 2025. https://www.pharmacytimes.com/view/fda-approves-epcoritamab-for-treatment-of-relapsed-refractory-follicular-lymphoma

4. First-in-human (FIH) trial in patients with relapsed, progressive or refractory B-cell lymphoma (EPCORE™ NHL-1). Clinicaltrials.gov. Updated November 4, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT03625037

5. FDA approves epcoritamab-bysp for follicular lymphoma indications. FDA. November 18, 2025. Accessed November 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications?utm_medium=email&utm_source=govdelivery