Epcoritamab

COPENHAGEN, Denmark I August 07, 2025 I Genmab A/S (Nasdaq: GMAB) today announced positive results of the Phase 3 EPCORE ® FL-1 trial evaluating subcutaneous epcoritamab, a bispecific antibody , in combination with rituximab and lenalidomide (R 2 ) versus R 2 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 pre-planned interim analysis, will be submitted for presentation at the 67 th Annual Meeting and Exposition of the American Society of Hematology (ASH) and will serve as the basis for global regulatory submissions. Separately, on July 24, the U.S. Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) for epcoritamab plus R 2 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 November 30, 2025. If approved, epcoritamab plus R 2 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. “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,” said Jan van de Winkel, Ph.D., 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 reinforces 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 R 2 in adult patients with R/R FL was consistent with the known safety profiles of the individual regimens (epcoritamab and R 2 ) and as presented in the U.S. prescribing information for epcoritamab. No new safety signals were observed. The U.S. 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 U.S. 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 U.S., EU or in any other territory. About Follicular Lymphoma (FL) FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30 percent of all cases. i About 15,000 people develop FL each year in the U.S. ii and it is considered incurable with current standard of care therapies. iii Patients often relapse and, with each relapse the remission and time to next treatment is shorter. iv Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25 percent of FL patients. v About the EPCORE FL-1 Trial EPCORE FL-1 ( NCT05409066 ) is a Phase 3 open-label interventional trial to evaluate the safety and efficacy of epcoritamab plus rituximab and lenalidomide (R 2 ) versus R 2 alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). The dual primary endpoints are ORR and PFS assessed by independent review committee (IRC) per Lugano criteria. About Epcoritamab Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody ® technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells. vi Epcoritamab (approved under the brand name EPKINLY ® in the U.S. and Japan, and TEPKINLY ® in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication. Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes five ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy ( NCT04628494 ), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL ( NCT05578976 ), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R 2 ) in patients with R/R FL ( NCT05409066 ), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R 2 ) compared to chemoimmunotherapy in patients with previously untreated FL ( NCT06191744 ), and a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL ( NCT06508658 ). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information. EPKINLY ® (epcoritamab-bysp) U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION What is EPKINLY? EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children. Please see Full Prescribing Information and Medication Guide , including Important Warnings. Globally, prescribing information varies; refer to the individual country product label for complete information. About Genmab Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO ® ) antibody medicines. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X . i Lymphoma Research Foundation official website. https://lymphoma.org/aboutlymphoma/nhl/fl/ . Accessed November 2024. ii Leukemia & Lymphoma Society. https://www.lls.org/research/follicular-lymphoma-fl . Accessed November 2024. iii Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica . 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421. iv Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol . 2018;184(5):753-759. doi:10.1111/bjh.15708. v Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin’s lymphoma. J Clin Oncol . 2008 Nov 10;26(32):5165-9. doi: 10.1200/JCO.2008.16.0283. Epub 2008 Oct 6. PMID: 18838711. vi Engelberts PJ, et al. DuoBody-CD3xCD20 Induces Potent T-Cell-Mediated Killing of Malignant B Cells in Preclinical Models and Provides Opportunities for Subcutaneous Dosing. EBioMedicine . 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625. SOURCE: Genmab