Genmab has announced positive results of the Phase III EPCORE FL-1 trial evaluating subcutaneous epcoritamab, a bispecific antibody, in combination with rituximab and lenalidomide (R2) versus R2 alone for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL).
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, reducing the risk of disease progression or death by 79%.
The results, derived from a preplanned interim analysis, will be submitted for presentation at the 67th Annual Meeting and Exposition of the American Society of Hematology (ASH) and will serve as the basis for global regulatory submissions.
Separately, on 24 July, the US Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) 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).
Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of 30 November 2025.
If approved, epcoritamab plus R2 would be the first bispecific antibody combination regimen available in the US as a second-line treatment option for patients with R/R FL.
“Although 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,” said Jan van de Winkel, PhD, Chief Executive Officer of Genmab.
“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.”
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 US prescribing information for epcoritamab.
No new safety signals were observed. The US 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.
The FDA also granted Breakthrough Therapy Designation (BTD) 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 US, EU or in any other territory.