On November 5, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ECHELON-2 trial evaluating ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with CD30-expressing peripheral T-cell lymphoma (PTCL) (Press release, Seattle Genetics, NOV 5, 2018, View Source [SID1234530737]). The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018 and full data will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 1-4, 2018 in San Diego, Calif. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL. ADCETRIS is currently not approved for the frontline treatment of PTCL.
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"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," said 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 PTCL who were treated with ADCETRIS 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 PTCL 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 3 ECHELON-2 clinical trial evaluated the combination of ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) compared to a recognized standard of care chemotherapy regimen, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL. 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 ADCETRIS 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 ADCETRIS plus CHP arm. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy. Full data will be presented at the ASH (Free ASH Whitepaper) Annual Meeting in the following session:
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
ECHELON-2 Phase 3 Clinical Trial Design
The randomized, double-blind, placebo-controlled phase 3 trial is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and was designed to enroll 450 patients, approximately 75 percent of whom were to be diagnosed with sALCL. The ECHELON-2 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.
Please see Important Safety Information at the end of this press release.
About T-Cell Lymphomas
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). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.
About ADCETRIS (brentuximab vedotin)
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
ADCETRIS injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.