SC Epcoritamab Combo Met ORR/PFS End Points in R/R Follicular Lymphoma

A Prescription Drug User Fee Act date of November 30, 2025, has been set, and if approved, the combination will be the first bispecific antibody combination available in the US as a second-line therapy for relapsed/refractory follicular lymphoma.

Treatment with subcutaneous epcoritamab-bysp (Epkinly), a bispecific antibody, combined with rituximab (Rituxan) and lenalidomide (Revlimid) in patients with relapsed/refractory follicular lymphoma met both dual primary end points set in the phase 3 EPCORE FL-1 trial (NCT05409066), according to a press release from the developer, Genmab.¹

A Prescription Drug User Fee Act date of November 30, 2025, has been set, and if approved, the combination will be the first bispecific antibody combination available in the US as a second-line therapy for relapsed/refractory follicular lymphoma.

The trial met the primary end points of overall response rate (ORR; P <.0001) and progression-free survival (PFS; HR, 0.21; P <.0001) assessed by independent review per Lugano criteria; the risk of disease progression and death was reduced by 79%. The developers noted that additional results from a pre-planned interim analysis will be submitted to be shared at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

Additionally, in July 2025, the FDA accepted and granted priority review to a supplemental biologics license application (sBLA) for epcoritamab plus rituximab and lenalidomide in patients with follicular lymphoma after at least 1 prior line of systemic therapy.

The sBLA was submitted based on statistically significant improvements to ORR (95.7%; P <.0001) and PFS (HR, 0.21; P <.0001).

“While therapeutic options exist for patients with relapsed/refractory follicular lymphoma, response rates tend to decline and durability diminishes with each subsequent line of treatment, which can increase the risk of the disease transforming into aggressive large-cell lymphoma,” stated Jan van de Winkel, PhD, chief executive officer of Genmab, in the press release.¹ “The results from this trial, and the decision from the FDA to accept the sBLA for priority review, demonstrate the potential of this epcoritamab combination therapy to reshape the treatment landscape and reinforce our shared commitment with AbbVie to advance epcoritamab as a potential core therapy across B-cell malignancies.”

EPCORE FL-1 is an open-label trial designed to compare the efficacy and safety of epcoritamab with rituximab and lenalidomide vs rituximab and lenalidomide alone in patients with relapsed/refractory follicular lymphoma.

In the investigational arm, patients received the recommended dose of epcoritamab in combination with rituximab and lenalidomide of 48 mg using a step-up dosing regimen to the full dose in cycle 1, with 28-day cycles.²

As of February 3, 2025, the trial had enrolled a total of 549 patients with histologically confirmed stage II, III, or IV classic follicular lymphoma with no evidence of histologic transformation to an aggressive lymphoma and CD20-positive disease on the most recent representative tumor biopsy based on the pathology report.³ Additional enrollment criteria include relapsed/refractory disease to at least 1 prior systemic regimen containing an anti-CD20 monoclonal antibody with chemotherapy, eligibility to receive rituximab and lenalidomide, and an ECOG performance status of 0 to 2.

Patients were excluded for having documented refractoriness to lenalidomide and lenalidomide exposure within 12 months prior to randomization.

The trial’s primary end points were ORR and PFS. Secondary end points included complete response rate, overall survival, minimal residual disease negativity rate, duration of response, duration of complete response, and time to progression, among others.

Regarding safety, the treatment combination demonstrated a toxicity profile consistent with previously known data of the independent regimens. No new safety signals were observed. It was noted in the release that the safety and efficacy of epcoritamab in combination with rituximab and lenalidomide is not approved in the US, EU, or any other territory, though clinical trials are underway, evaluating the combination.

References

1. Genmab announces phase 3 EPCORE® FL-1 clinical trial met dual primary endpoints in patients with relapsed/refractory (R/R) follicular lymphoma (FL). News release. Genmab. August 7, 2025. Accessed August 8, 2025. https://tinyurl.com/4nhj3566
2. Falchi L, Morschhauser F, Linton K, et al. EPCORE FL-1: phase 3 trial of subcutaneous epcoritamab with rituximab and lenalidomide (R²) vs R² alone in patients with relapsed or refractory follicular lymphoma. Blood. 2023;142(suppl_1):3053. doi:10.1182/blood-2023-180092
3. 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). ClincialTrials.gov. Updated July 28, 2025. Accessed August 8, 2025. https://tinyurl.com/254t76mu