EPCORE FL-1 phase III trial results show that subcutaneous epcoritamab in combination with rituximab and lenalidomide reduced the risk of disease progression or death by 79% for patients with relapsed/refractory follicular lymphoma.
The open-label interventional trial compared subcutaneous epcoritamab, a bispecific antibody, in combination with rituximab and lenalidomide versus R2 alone for the treatment of adult patients.
Subcutaneous epcoritamab is sponsored by Genmab.
The study met its dual primary endpoints of overall response rate (ORR, p-value < 0.0001) and progression-free survival (PFS, HR 0.21, p-value <0.0001), demonstrating statistically significant and clinically meaningful differences in both endpoints. They were assessed by an independent review committee, per Lugano criteria.
The results, derived from a pre-planned interim analysis, will be submitted for presentation at the 67th Annual Meeting and Exposition of the American Society of Hematology and will serve as the basis for global regulatory submissions.
“While therapeutic options exist for patients with relapsed or 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,” Jan van de Winkel, CEO of Genmab, said in a statement. “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 reinforces our shared commitment with AbbVie to advance epcoritamab as a potential core therapy across B-cell malignancies.”
FDA also accepted for priority review the supplemental Biologics License Application for epcoritamab plus R2 following at least one prior systemic therapy.
The sBLA submission was based on data from a first interim analysis that demonstrated statistically significant improvements in ORR (95.7%, p-value < 0.0001) and PFS (HR 0.21, p-value <0.0001, based on the intent-to-treat population).
FDA has set a target action date of November 30. If approved, epcoritamab plus R2 would be the first bispecific antibody combination regimen available in the U.S. as a second-line treatment option for patients with R/R FL.
The safety profile of epcoritamab in combination with R2 in adult patients with R/R FL was consistent with the known safety profiles of the individual regimens (epcoritamab and R2) and as presented in the U.S. prescribing information for epcoritamab. No new safety signals were observed.
In addition, FDA has granted accelerated approval of single agent epcoritamab for the treatment of adults with R/R FL after two or more lines of systemic therapy. FDA also granted Breakthrough Therapy Designation to epcoritamab in combination with R2 for the treatment of adult patients with R/R FL who have received at least one prior line of therapy. The safety and efficacy of epcoritamab in combination with R2 in R/R FL is currently being evaluated in clinical trials and is not approved or established in the U.S., EU or in any other territory.
FL is typically an indolent form of non-Hodgkin’s lymphoma that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases. About 15,000 people develop FL each year in the U.S. and it is considered incurable with current standard of care therapies.
Patients often relapse, and with each relapse, the remission and time to next treatment is shorter. Over time, transformation to diffuse large B-cell lymphoma, an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.
