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Enrollment Completed for Phase III ECHELON-2 Clinical Trial Evaluating Front-Line Brentuximab Vedotin in Mature T-Cell Lymphoma

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Seattle Genetics, Inc, and Takeda Pharmaceutical Company Limited have announced completion of patient enrollment in the ECHELON-2 clinical trial. ECHELON-2 is a global phase III randomized trial evaluating brentuximab vedotin (Adcetris) as part of a front-line combination chemotherapy regimen in patients with previously untreated CD30-positive mature T-cell lymphoma. Brentuximab vedotin is an antibody-drug conjugate directed at CD30, which is expressed on several types of non-Hodgkin lymphoma, including subsets of mature T-cell lymphoma, as well as Hodgkin lymphoma. Brentuximab vedotin is currently not approved for the front-line treatment of mature T-cell lymphoma.

Patients in ECHELON-2 were randomized to receive a novel combination regimen consisting of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone vs cyclophosphamide, doxorubicin, vincristine, and prednisone, the recognized standard-of-care treatment regimen for front-line mature T-cell lymphoma. The trial enrolled 452 patients.

The ECHELON-2 trial is being conducted under a Special Protocol Assessment agreement from the U.S. Food and Drug Administration. The trial also received European Medicines Agency scientific advice.

“Our goal is to establish brentuximab vedotin as the foundation of care for CD30-expressing lymphomas and redefine front-line treatment in Hodgkin lymphoma and mature T-cell lymphoma through our broad, late-stage clinical development program currently underway. The ECHELON-2 clinical trial represents our fourth phase III study to complete enrollment,” said Naomi Hunder, MD, Vice President, Clinical Development at Seattle Genetics. “We look forward to the results of the ECHELON-2 front-line MTCL study in the 2017 to 2018 time frame.…”

“Mature T-cell lymphoma is a rare, aggressive type of cancer in which the standard-of-care chemotherapy regimen has not changed in decades,” said Dirk Huebner, MD, Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “Achieving target enrollment represents a key milestone for ECHELON-2 as we evaluate the efficacy and safety of brentuximab vedotin in newly diagnosed mature T-cell lymphoma patients, and to our ultimate goal of bringing important new therapies to patients with CD30-positive malignancies.”

Previous Findings

Data from a phase I trial evaluating brentuximab vedotin plus cyclophosphamide/doxorubicin/prednisone in mature T-cell lymphoma were previously presented at the American Society of Hematology (ASH) Annual Meetings in 2012 and 2015. Data demonstrated that 26 of 26 patients (100%) achieved an objective response, including 23 (88%) with a complete remission and 3 (12%) with a partial remission.

Long-term follow-up data estimated the 3-year overall survival was 80% and 3-year progression-free survival was 52%, with no patients receiving a consolidative stem cell transplant in first remission. Three-year overall survival and progression-free survival rates of less than 40% and 30%, respectively, have previously been reported for patients in this setting treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (Reimer et al, J Clin Oncol 27: 106-113; 2009; Fanale et al, J Clin Oncol 32: 3137-3143; 2014).

The most common adverse events of any grade occurring in more than 30% of patients in this phase I trial were peripheral sensory neuropathy, diarrhea, fatigue, and hair loss. Additional 4-year follow-up data from this trial will be presented in a poster presentation at the 2016 ASH Annual Meeting.

ECHELON-2 Trial Design

The double-blind, placebo-controlled global phase III trial is investigating brentuximab vedotin plus cyclophosphamide/doxorubicin/prednisone vs cyclophosphamide/doxorubicin/vincristine/prednisone as front-line therapy in patients with CD30-positive mature T-cell lymphoma. The primary endpoint is progression-free survival per independent review facility assessment using the Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Secondary endpoints include overall survival, complete remission rate, and safety.

The multicenter trial is being conducted in North America, Europe, and Asia. The study has enrolled 452 patients, with approximately 225 patients per treatment arm. Data from the trial will be available when a prespecified number of progression-free survival events have occurred.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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