Supplemental Biologics License Application for Brentuximab Vedotin in Frontline Treatment of CD30-Expressing Peripheral T-Cell Lymphomas Submitted to US FDA
Published on 06th November
Seattle Genetics has submitted a supplemental Biologics License Application (BLA) for brentuximab vedotin (Adcetris®) to the U.S. Food and Drug Administration (FDA).
The submission is based on data from the phase III ECHELON-2 trial evaluating brentuximab vedotin in combination with chemotherapy for the frontline treatment of patients with CD30-expressing peripheral T-cell lymphoma (PTCL). The positive topline results of the Phase III ECHELON-2 clinical trial were announced in October 2018 and full data will be presented at the upcoming annual meeting of the American Society of Hematology (ASH), held December 1-4, 2018 in San Diego, California.
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing).
Results from the ECHELON-2 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival and importantly, overall survival, in patients with previously untreated CD30-expressing peripheral T-cell lymphoma who were treated with [brentuximab vedotin] in combination with CHP chemotherapy over standard of care CHOP chemotherapy.
Peripheral T-cell lymphoma, which accounts for approximately 10% of non-Hodgkin lymphoma cases in the United States and Europe and may be as high as 24% in parts of Asia, is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer (NK) cells.
The disease is classified as a subtype of non-Hodgkin’s lymphoma (NHL). NHL affects two particular types of white blood cells: B-cells and T-cells. Peripheral T-cell lymphoma specifically affects T-cells, and results when T-cells develop and grow abnormally.
It is the origin of the disease in the lymphatic system that gave it the name peripheral T-cell lymphoma. In the case of peripheral T-cell lymphoma, the term “peripheral” does not refer to the extremities, but identifies the disease as a cancer that arises in the lymphoid tissues outside of the bone marrow such as lymph nodes, spleen, gastrointestinal tract, and skin.
The proposed treatment option, brentuximab vedotin, is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of peripheral T-cell lymphoma. The drug, which is on of four approved and commercially available antibody-drug conjugates is currently not approved for the frontline treatment of patients with peripheral T-cell lymphoma.
“CD30 is expressed in several subtypes of peripheral T-cell lymphoma, an aggressive type of non-Hodgkin lymphoma, and the current standard of care for frontline treatment consisting of a multi-agent chemotherapy regimen called CHOP has not changed in several decades,” explained Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.
“Results from the ECHELON-2 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival and importantly, overall survival, in patients with previously untreated CD30-expressing peripheral T-cell lymphoma who were treated with [brentuximab vedotin] in combination with CHP chemotherapy over standard of care CHOP chemotherapy. We believe these superior results over standard of care represent a significant advance for patients with CD30-expressing peripheral T-cell lymphoma and for the medical community, and we look forward to working with the FDA during the review process of this application to bring this potential new treatment regimen to patients as quickly as possible.”
The phase III ECHELON-2 clinical trial evaluated the combination of [brentuximab vedotin] plus CHP (cyclophosphamide, doxorubicin, prednisone) compared to a recognized standard of care chemotherapy regimen, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing peripheral T-cell lymphoma. The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110).
The brentuximab vedotin plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the brentuximab vedotin plus CHP arm. The safety profile of brentuximab vedotin plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of brentuximab vedotin in combination with chemotherapy.
Oral Session: Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: T-Cell Lymphoma: Chemotherapy and Targeted Approaches (Abstract #997) | Date/Location: Monday, December 3, 2018 at 6:15 p.m. PT, San Diego Convention Center, Room 6F | Presenter: Steven Horwitz, M.D.,Department of Medicine, Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York.
Last Editorial Review: November 6, 2018
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