Health Canada Approves Epcoritamab Triplet for Relapsed or Refractory Follicular Lymphoma
Key Insights
Health Canada issued a Notice of Compliance for epcoritamab (Epkinly) plus lenalidomide and rituximab in adults with relapsed or refractory grade 1, 2 or 3a follicular lymphoma (search) after at least one prior systemic line.
The approval rests on the phase 3 EPCORE FL-1 trial, in which the epcoritamab regimen cut the risk of disease progression or death by 79% versus lenalidomide and rituximab alone.
Updated EPCORE FL-1 subgroup data showed an overall response rate of 95% versus 79% and complete response rates of 83% versus 50% for the triplet.
Health Canada has issued a Notice of Compliance for epcoritamab (Epkinly) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) for adults with relapsed or refractory grade 1, 2 or 3a follicular lymphoma (search) who have received at least one prior line of systemic therapy, according to a news release from developer AbbVie.
Follicular lymphoma (search) is a typically slow-growing form of non-Hodgkin lymphoma that often returns after treatment. Approximately 2,400 to 3,000 Canadians are diagnosed with FL each year.
EPCORE FL-1 Efficacy
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 Annual Meeting and Exposition. The study enrolled 488 adults with relapsed or refractory follicular lymphoma (search) following at least one prior line of systemic therapy.
Adding epcoritamab to lenalidomide and rituximab reduced the risk of disease progression or death by 79% compared with lenalidomide and rituximab alone, with a hazard ratio of 0.21 (95% CI: 0.13-0.33; p<0.0001).
"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," said Laurie Sehn, MD, MPH, clinical professor of medicine in the Division of Medical Oncology at BC Cancer and the University of British Columbia.
Trial Design and Dosing
In the open-label EPCORE FL-1 trial, patients with histologically confirmed CD20 (search)-positive relapsed or refractory follicular lymphoma (search) were randomly assigned 1:1 to receive lenalidomide and rituximab with or without subcutaneous epcoritamab.
Epcoritamab was given as three weekly step-up doses during cycle 1, then weekly at the full dose in cycles 2 and 3, and every four weeks in cycles 4 through 12. Rituximab was administered at 375 mg/m² weekly in cycle 1 and every four 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 and progression-free survival, both assessed by an independent review committee. Secondary end points included complete response rate, overall survival and safety.
Subgroup Response and Safety
A subgroup analysis of EPCORE FL-1 presented at the European Hematology Association 2026 Congress showed that the epcoritamab regimen produced an overall response rate of 95% versus 79% with lenalidomide and rituximab alone. Complete response rates were 83% versus 50%, respectively, and the hazard ratio for progression-free survival was 0.21 (95% CI: 0.14-0.31).
The benefit held across clinically relevant subgroups. Among patients younger than 70 years, the hazard ratio for progression-free survival 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). The hazard ratio was 0.20 (95% CI: 0.12-0.34) in patients with one prior line of therapy and 0.24 (95% CI: 0.13-0.42) in those who received at least two prior lines.
Grade 3 or higher treatment-emergent adverse events were more frequent with the epcoritamab regimen in both age groups. They occurred in 89% versus 64% of patients younger than 70 years and in 93% versus 76% of those 70 years or older. Treatment-emergent adverse events led to treatment discontinuation in 15% versus 10% and 31% versus 17% of patients in these groups, respectively.
Mechanism and Regulatory History
Epcoritamab is a subcutaneously administered bispecific antibody designed to connect T cells with B cells, including the abnormal B cells involved in follicular lymphoma (search), to help the immune system target the cancer cells. The treatment is being co-developed by AbbVie and Genmab under their oncology collaboration, and the companies continue to evaluate epcoritamab alone and in combination with other treatments across a range of blood cancers.
In the United States, the FDA approved epcoritamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (search) in November 2025. Concurrently, the FDA granted traditional approval to epcoritamab monotherapy for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy, an indication that had received accelerated approval in 2024.
In the FDA's review of EPCORE FL-1, median progression-free survival was not reached with the epcoritamab regimen versus 11.2 months with lenalidomide and rituximab alone, and the overall response rate was 89% versus 74%, respectively. The US prescribing information carries boxed warnings for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.