Epcoritamab Combo Receives Canadian Approval in R/R Follicular Lymphoma

Health Canada has issued a Notice of Compliance for epcoritamab (Epkinly) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) for adults with relapsed/refractory grade 1, 2, or 3a follicular lymphoma who have received at least 1 prior line of systemic therapy, according to a news release from the developer, AbbVie.¹

The authorization is supported by findings from the phase 3 EPCORE FL-1 trial (NCT05409066), with updated findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.² In that trial, adding epcoritamab to lenalidomide and rituximab reduced the risk of disease progression or death by 79% vs lenalidomide and rituximab alone.

What data supported Health Canada’s approval of epcoritamab?

EPCORE FL-1 enrolled 488 adults with relapsed/refractory follicular lymphoma who had received at least 1 prior line of systemic therapy. In the trial, the epcoritamab regimen significantly improved progression-free survival (PFS) compared with lenalidomide and rituximab alone (HR, 0.21; 95% CI, 0.13-0.33; P < .0001).

“The positive results from EPCORE FL-1 show that adding epcoritamab to lenalidomide and rituximab significantly reduces the risk of lymphoma progression or death. Having a novel and more effective treatment option after prior therapy is important for patients living with this recurring disease,” Laurie Sehn, MD, MPH, clinical professor of medicine in the Division of Medical Oncology at BC Cancer and the University of British Columbia, stated in the press release.¹

What is the EPCORE FL-1 trial design?

In the open-label EPCORE FL-1 trial, patients with histologically confirmed CD20-positive relapsed/refractory follicular lymphoma were randomly assigned 1:1 to receive lenalidomide and rituximab with or without subcutaneous epcoritamab. Epcoritamab was given as 3 weekly step-up doses during cycle 1, then weekly at the full dose in cycles 2 and 3, and every 4 weeks in cycles 4 through 12. Rituximab was administered at 375 mg/m² weekly in cycle 1 and every 4 weeks in cycles 2 through 5. Lenalidomide was given at 20 mg daily for up to 12 cycles.

The dual primary end points were overall response rate (ORR) and PFS, both assessed by an independent review committee. Secondary end points included complete response (CR) rate, overall survival, and safety.

How did epcoritamab perform across patient subgroups?

A subgroup analysis of EPCORE FL-1 presented at the European Hematology Association (EHA) 2026 Congress showed that the epcoritamab regimen produced an ORR of 95% vs 79% with lenalidomide and rituximab alone.³ CR rates were 83% vs 50%, respectively, and the HR for PFS was 0.21 (95% CI, 0.14-0.31).

The benefit held across clinically relevant subgroups. Among patients younger than 70 years, the HR for PFS was 0.19 (95% CI, 0.12-0.31); among those 70 years or older, it was 0.29 (95% CI, 0.14-0.60). Additionally, the HR for PFS was 0.20 (95% CI, 0.12-0.34) in patients with 1 prior line of therapy and 0.24 (95% CI, 0.13-0.42) in those who received at least 2 prior lines.

Grade 3 or higher treatment-emergent adverse effects (TEAEs) were more frequent with the epcoritamab regimen in both age groups. They occurred in 89% vs 64% of patients younger than 70 years and in 93% vs 76% of those 70 years or older. TEAEs led to treatment discontinuation in 15% vs 10% and 31% vs 17% of patients in these groups, respectively.

What is epcoritamab’s regulatory history?

Epcoritamab is a subcutaneously administered bispecific antibody. It is designed to connect T cells with B cells, including the malignant B cells involved in follicular lymphoma, to help the immune system target them.

In the US, the FDA approved epcoritamab plus lenalidomide and rituximabfor relapsed/refractory follicular lymphoma in November 2025.⁴ Concurrently, the FDA granted traditional approval to epcoritamab monotherapy for relapsed/refractory follicular lymphoma after 2 or more lines of systemic therapy, an indication that had received accelerated approval in 2024.

In the FDA’s review of EPCORE FL-1, the median PFS was not reached with the epcoritamab regimen vs 11.2 months with lenalidomide and rituximab alone, and the ORR was 89% vs 74%, respectively. The US prescribing information carries boxed warnings for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome.

References

1. EPKINLY® receives Health Canada approval for adults with follicular lymphoma. News release. AbbVie Canada. September 24, 2026. Accessed September 24, 2026. https://tinyurl.com/bs68rmyv
2. Falchi L, Nijland M, Huang H, et al. 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. Blood. 2025;146(supplement 1):466. doi:10.1182/blood-2025-466
3. Nijland M, Falchi L, Linton K, et al. Clinically relevant subgroup analysis from the randomized phase 3 EPCORE FL-1 trial: treatment (tx) effect of epcoritamab with lenalidomide and rituximab (R²) in R/R follicular lymphoma (FL). Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S229.
4. FDA approves epcoritamab-bysp for follicular lymphoma indications. News release. FDA. November 18, 2025. Accessed September 24, 2026. https://tinyurl.com/4pejyct8