sBLA Submission Planned for Epcoritamab/Rituximab/Lenalidomide in R/R FL

R/R Follicular Lymphoma

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A supplemental biologics application (sBLA) will be submitted to the FDA in the first half of 2025 seeking the approval of subcutaneous epcoritamab-bysp (Epkinly) plus rituximab (Rituxan) and lenalidomide (Revlimid) for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) who have received 1 or more prior lines of therapy.1

Genmab, the developer of epcoritamab, has decided to submit the sBLA based on positive topline data from the phase 3 EPCORE FL-1 trial (NCT05409066) investigating epcoritamab plus rituximab and lenalidomide vs rituximab plus lenalidomide alone in adult patients with relapsed/refractory FL. An interim analysis performed by an Independent Data Monitoring Committee review reported that the trial met one of its dual primary end points: overall response rate (ORR; P < .0001).

Furthermore, the safety profile of the triplet 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 (US) prescribing information for epcoritamab. Additionally, investigators observed no new safety signals, according to a news release.

Findings from EPCORE FL-1 will be submitted later in 2025 for presentation at an upcoming medical meeting and will be discussed with global regulatory authorities.

“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,” Jan van de Winkel, PhD, chief executive officer of Genmab, stated in the news release. “The interim topline results demonstrate the potential of this investigational epcoritamab combination regimen to treat relapsed or refractory [patients with] FL. 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.”

The open-label EPCORE FL-1 trial enrolled patients at least 18 years of age with histologically confirmed classic, stage II to IV FL with no evidence of histologic transformation to an aggressive lymphoma and CD20-positive disease on the most recent representative tumor biopsy per the pathology report.2 Patients needed to have disease that was relapsed or refractory to at least 1 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 excluded if they had documented refractoriness to lenalidomide or if they had been exposed to lenalidomide within 12 months prior to random assignment.

Patients were randomly assigned to receive subcutaneous epcoritamab at 1 of 2 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 end points are independent review committee (IRC)–assessed ORR and progression-free survival (PFS). Secondary end points include complete response (CR) rate, overall survival, minimal residual disease negativity rate, investigator-assessed PFS, investigator assessed ORR, duration of response, duration of CR, time to progression, time to next anti-lymphoma treatment, CR rate at end of treatment, time to response, time to CR, event-free survival, and quality of life outcomes.

Notably, in June 2024, the FDA granted accelerated approval to epcoritamab monotherapy for the treatment of adult patients with relapsed/refractory FL who have received at least 2 prior lines of systemic therapy.3

References

1. Genmab to submit supplemental biologics license application (sBLA) to U.S. Food and Drug Administration for epcoritamab plus rituximab and lenalidomide (R2) in patients with relapsed/refractory follicular lymphoma (FL). News release. Genmab. May 2, 2025. Accessed May 2, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-submit-supplemental-biologics-license-application-sbla-us
2. 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 March 21, 2025. Accessed May 2, 2025. https://clinicaltrials.gov/study/NCT05409066
3. FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma. FDA. June 26, 2024. Accessed May 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-follicular-lymphoma