Genmab and AbbVie Submit Regulatory Applications for Epcoritamab Bispecific Antibody in Relapsed/Refractory B-Cell Lymphomas
核心洞察
Genmab submitted a Biologics License Application to the FDA for subcutaneous epcoritamab to treat relapsed/refractory large B-cell lymphoma (搜索) after two or more lines of systemic therapy.
AbbVie (搜索)'s Marketing Authorization Application for epcoritamab in relapsed/refractory diffuse large B-cell lymphoma (搜索) has been validated by the European Medicines Agency (搜索).
The regulatory submissions are supported by results from the pivotal EPCORE NHL-1 Phase 2 trial evaluating epcoritamab's safety and efficacy in patients with CD20 (搜索)+ mature B-cell non-Hodgkin lymphoma (搜索).
Genmab A/S and AbbVie (搜索) have submitted regulatory applications for epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous bispecific antibody, marking a significant milestone in the development of novel treatments for relapsed/refractory B-cell lymphomas. Genmab submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory large B-cell lymphoma (搜索) (LBCL) after two or more lines of systemic therapy, while AbbVie's Marketing Authorization Application (MAA) for relapsed/refractory diffuse large B-cell lymphoma (搜索) (DLBCL) has been validated by the European Medicines Agency (搜索) (EMA).
Clinical Trial Foundation
The regulatory submissions are supported by previously announced results from the LBCL cohort of the pivotal EPCORE NHL-1 open-label, multi-center Phase 2 clinical trial. The study evaluated the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20 (搜索)+ mature B-cell non-Hodgkin lymphoma (搜索) (B-NHL), including DLBCL. These results were presented in a late-breaking oral presentation as part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA2022) in Vienna, Austria.
The EPCORE NHL-1 trial includes a Phase 1 first-in-human dose escalation part, a Phase 2 expansion part, and an optimization part. The primary endpoint of the Phase 2 expansion part was overall response rate (ORR) as assessed by an independent review committee (IRC). Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity.
Addressing Unmet Medical Need
"Even with existing therapies to treat these lymphomas, there is a significant medical need for alternative and accessible treatment options for patients who are unable to tolerate current treatments or whose treatments have failed," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Together with our partner AbbVie (搜索), we believe epcoritamab has the potential to become a core therapy for patients with B-cell malignancies, and the submission of these regulatory applications to the FDA and EMA is an important step in potentially bringing epcoritamab to people living with relapsed/refractory B-cell lymphomas."
Mohamed Zaki, M.D., Ph.D., vice president and head of global oncology development at AbbVie (搜索), emphasized the significance of these submissions: "The regulatory submissions for epcoritamab exemplify our pursuit to deliver innovative care for people living with large B-cell lymphoma (搜索) and diffuse large B-cell lymphoma (搜索) who have limited treatment options. This achievement represents an initial step in our commitment to scientific research and providing an important treatment option with the potential to become a core therapy for people living with B-cell malignancies such as LBCL and DLBCL."
Disease Background and Burden
Large B-cell lymphoma (搜索) (LBCL) is a fast-growing type of non-Hodgkin's lymphoma (NHL), a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally. Diffuse large B-cell lymphoma (搜索) (DLBCL) is the most common type of NHL worldwide, accounting for approximately 30-31 percent of all NHL cases. DLBCL can arise in lymph nodes as well as in organs outside of the lymphatic system, occurs more commonly in the elderly and is slightly more prevalent in men.
Mechanism of Action
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology. The DuoBody-CD3 (搜索) 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 (搜索) on B-cells, inducing T-cell mediated killing of CD20+ cells. CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma (搜索), follicular lymphoma (搜索), mantle cell lymphoma (搜索) and chronic lymphocytic leukemia (搜索).
Development Partnership and Future Plans
Epcoritamab is being co-developed by Genmab and AbbVie (搜索) 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. The companies are committed to evaluating epcoritamab as a monotherapy and in combination across lines of therapy in a range of hematologic malignancies.
Current ongoing studies include a Phase 3, open-label, randomized clinical trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory DLBCL (NCT: 04628494) and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with relapsed/refractory follicular lymphoma (搜索) (FL) (NCT: 05409066).