Genmab has announced plans to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in the first half of 2025 for epcoritamab (Epkinly) in combination with rituximab and lenalidomide. The application targets the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma who have received one or more prior lines of therapy.
The decision follows positive interim results from the phase 3 EPCORE FL-1 trial, which evaluated epcoritamab plus rituximab and lenalidomide (R2) compared to R2 alone. According to an Independent Data Monitoring Committee review, the study met one of its dual primary endpoints of overall response rate with high statistical significance (P < .0001).
"We are pleased with the strength of the data that allows us to submit an sBLA in accordance with the US FDA's Project Frontrunner, which supports our commitment to advance novel medicines to patients who need them," said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. "The interim topline results demonstrate the potential of this investigational epcoritamab combination regimen to treat relapsed or refractory [patients with] FL."
Mechanism of Action and Development Partnership
Epcoritamab is a subcutaneously administered IgG1-bispecific antibody that redirects cytotoxic T-cells to target malignant B-cells. The therapy represents a key asset for Genmab, which specializes in antibody-based cancer therapies and is being developed in collaboration with AbbVie.
The safety profile of the triplet combination was reported to be consistent with the known safety profiles of both epcoritamab and rituximab plus lenalidomide, as well as with the safety data published in the United States prescribing information for epcoritamab. No new safety signals were observed during the trial.
EPCORE FL-1 Trial Design
The open-label EPCORE FL-1 trial (NCT05409066) enrolled patients at least 18 years of age with histologically confirmed classic, stage II to IV follicular lymphoma with no evidence of histologic transformation to an aggressive lymphoma and CD20-positive disease on the most recent representative tumor biopsy.
Eligible patients had disease that was relapsed or refractory to at least one prior systemic therapy regimen containing an anti-CD20 monoclonal antibody plus chemotherapy. Additional eligibility criteria included an ECOG performance status of 0 to 2, eligibility to receive lenalidomide plus rituximab per investigator discretion, and an estimated creatinine clearance level of at least 50 mL per minute.
Patients were randomly assigned to receive subcutaneous epcoritamab at one of two dose levels in combination with oral lenalidomide 20 mg plus intravenous rituximab at 375 mg/m² for 12 28-day cycles, or lenalidomide plus rituximab alone at the same treatment frequency.
The coprimary endpoints are independent review committee (IRC)–assessed overall response rate and progression-free survival (PFS). Secondary endpoints include complete response rate, overall survival, minimal residual disease negativity rate, and various time-to-event measures.
Current Regulatory Status
Notably, epcoritamab already received accelerated FDA approval in June 2024 as a monotherapy for the treatment of adult patients with relapsed/refractory follicular lymphoma who have received at least two prior lines of systemic therapy. The current sBLA submission aims to expand the indication to include patients who have received just one prior line of therapy and to establish the efficacy of the combination regimen.
Full results from the EPCORE FL-1 trial are expected to be submitted later in 2025 for presentation at an upcoming medical meeting and will be shared with global regulatory authorities.
"This milestone represents our commitment to the ongoing development of epcoritamab, with our partner AbbVie, and we look forward to seeing the full results from the study," van de Winkel added.
Clinical Significance
Follicular lymphoma is a common form of indolent non-Hodgkin lymphoma characterized by slow growth and a high rate of relapse. Despite numerous treatment options, patients with relapsed or refractory disease face diminishing returns with subsequent lines of therapy, highlighting the need for novel treatment approaches.
The potential approval of epcoritamab in combination with rituximab and lenalidomide would provide an important new option for patients earlier in their treatment journey, potentially delaying disease progression and improving outcomes for this difficult-to-treat patient population.
