Tahi Ahmadi and Asud Khaliq Share their Views on EPKINLY (epcoritamab) U.S. FDA Approval in DLBCL

Shots:

Tahi and Asud initiated the conversation with an overview of EPKINLY^TM(epcoritamab) and its approval by the U.S. FDA to treat R/R DLBCL
They then spoke about the study design and results from the EPCORE NHL-1 P-I/II trial that served as the basis for the U.S. FDA approval of EPKINLY.
EPKINLY is being co-developed and co-commercialized by Genmab and AbbVie. Both companies are evaluating epcoritamab as a monotherapy and in different combinations to treat hematologic malignancies

*Tahi Ahmadi, Executive Vice President & Chief Medical Officer, Head of Experimental Medicines at Genmab

Asud Khaliq, Therapeutic Area Head, Solid Tumors and Genmab Collaboration, U.S. Medical Affairs, AbbVie

Smriti: Tell me about EPKINLY^TM(epcoritamab-bysp).

Tahi Ahmadi and Asud Khaliq: EPKINLY, the first and only T-cell engaging bispecific antibody administered subcutaneously, was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2023, for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma, after two or more lines of systemic therapy. EPKINLY was approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s). EPKINLY is being co-developed and co-commercialized by Genmab and AbbVie as part of the companies’ oncology collaboration.

EPKINLY is a IgG1-bispecific antibody administered subcutaneously that was created using Genmab's proprietary DuoBody^® technology. Genmab's DuoBody^®-CD3 technology is designed to direct cytotoxic T-cells selectively to elicit an immune response toward target cell types.

EPKINLY is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells and induces 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 large B-cell lymphoma (LBCL) and its subtype DLBCL, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia.

Smriti: Please discuss the clinical trial data that served as the basis for the U.S. FDA approval of EPKINLY.

Tahi Ahmadi and Asud Khaliq: The FDA approval was based on the results from the Phase 1/2 EPCORE™ NHL-1 study. In the study, subcutaneous EPKINLY monotherapy demonstrated responses in challenging-to-treat, relapsed or refractory DLBCL patients who have received at least two prior treatments. An overall response (complete or partial response) was seen in 61 percent (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38 percent (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The estimated median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).

In the study, 157 patients with LBCL were enrolled. Among them, 148 patients with DLBCL or high-grade B-cell lymphoma (HGBCL) were enrolled, 86 percent of which were diagnosed with DLBCL NOS, including 27 percent with DLBCL transformed from indolent lymphoma, and 14 percent with HGBCL. The median number of prior therapies was three (range: 2 to 11), with 30 percent receiving two prior therapies, 30 percent receiving three prior therapies, and 40 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation (HSCT), and 39 percent had prior chimeric antigen receptor (CAR) T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy. EPKINLY delivered an overall response rate of 61 percent, a complete response rate of 38 percent and median duration of response of 15.6 months in heavily pretreated R/R DLBCL patients.

The approval of EPKINLY in the U.S. is an important milestone for those with R/R DLBCL, and we’re committed to further evaluating and developing epcoritamab as a potential future core therapy across B-cell malignancies.

Smriti: Why is the approval of EPKINLY meaningful for patients with DLBCL?

Tahi Ahmadi and Asud Khaliq: Historically, DLBCL patients who are refractory to current therapies, or who have relapsed following intense treatment, have limited treatment options and face unique challenges in managing this aggressive disease. Subcutaneous EPKINLY addresses the need for an efficacious, tolerable, accessible treatment for R/R DLBCL patients after two or more lines of systemic therapy.

Smriti: Are you in or planning to indulge in a collaboration with other organizations for the development and commercialization of epcoritamab?

Tahi Ahmadi and Asud Khaliq: We have no specific plans for further collaboration for the development and commercialization of epcoritamab outside of the Genmab/AbbVie partnership. Together we are committed to further developing epcoritamab and delivering safe and effective therapies to treat hematologic malignancies as part of our companies’ oncology research collaboration.

Smriti: What other geographical locations do you plan to seek approval for epcoritamab?

Tahi Ahmadi and Asud Khaliq: We are pleased that the EMA has validated our Marketing Authorization Application (MAA) for epcoritamab for the treatment of R/R DLBCL after two or more lines of systemic therapy. Additionally, in December 2022, Genmab announced the submission of a Japan New Drug Application (JNDA) for epcoritamab for the treatment of R/R LBCL after two or more lines of systemic therapy.

Smriti: Are you planning to explore the potential benefits of epcoritamab for other indications and/or combinations as well?

Tahi Ahmadi and Asud Khaliq: Genmab and AbbVie are evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes an ongoing Phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494), an ongoing phase 3, open-label, randomized trial evaluating epcoritamab in combination in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (NCT: 05409066).

We are committed to exploring the potential of epcoritamab as a core therapy for patients across the spectrum of B-cell malignancies.

Smriti: Are there any other products being developed in your pipeline to treat lymphomas or other indications?

Tahi Ahmadi and Asud Khaliq: Both companies are committed to researching and developing safe and effective therapies to treat hematologic malignancies. You can learn more about our pipelines at Genmab.com and AbbVie.com.

Image Source: Canva

About the Authors:

Tahi Ahmadi

Tahi Ahmadi is the Executive Vice President & Chief Medical Officer, Head of Experimental Medicines at Genmab. Dr. Ahmadi is a registered manager of Genmab with the Danish Business Authority. He holds an M.D. from the University of Cologne (Germany) and a Ph.D. from the University of Freiburg (Germany) and has expertise in translational research, strategic product development, global regulatory submissions and clinical development. Dr. Ahmadi is also an author on a number of scientific articles that have been published in journals such as NEJM, Lancet, JCO and Blood, among others.

Asud Khaliq

Asud Khaliq is the Therapeutic Area Head, Solid Tumors and Genmab Collaboration, U.S. Medical Affairs at AbbVie. Previously, he served as Head of Medical Affairs, Imbruvica Genmab Collaboration Solid Tumors at AbbVie, where he led a cross-functional Medical Affairs team delivering Medical Affairs strategies and plans for Imbruvica and the company’s hematology pipeline across multiple indications. He received his Biochemistry, PhD Cell Biology, Cancer degree at The University of Manchester.