The FINANCIAL — Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited on October 28 announced that the companies have achieved completion of target patient enrollment in the phase 3 ECHELON-1 clinical trial.
ECHELON-1 is a randomized trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in patients with previously untreated advanced classical Hodgkin lymphoma (HL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. ADCETRIS is currently not approved for the frontline treatment of HL, according to Takeda.
Patients in ECHELON-1 were randomized to receive either ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard of care for frontline HL, or a novel combination consisting of ADCETRIS+AVD, which removes bleomycin from the regimen. The trial has enrolled approximately 1,300 patients, although it remains open at select sites to complete enrollment of approximately 20 patients in an additional cohort to fulfill an ex-U.S. regulatory commitment related to measurement of drug levels during treatment (pharmacokinetics). This continued enrollment will not affect the expected timing of data readout from the trial in the 2017 to 2018 timeframe, based on anticipated event rates. The ECHELON-1 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.
“In the majority of the world, the standard of care for newly diagnosed Hodgkin lymphoma has not changed in more than three decades, and is based on the globally recognized ABVD regimen of four chemotherapy drugs. With the ECHELON-1 clinical trial, our goal is to redefine the standard of care with a novel ADCETRIS-based combination treatment regimen that improves patient outcomes with a manageable safety profile,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We look forward to reporting results from the ECHELON-1 trial to potentially support an ADCETRIS supplemental Biologics License Application seeking a label expansion for use in this setting.”
“Approximately 25 percent of newly diagnosed Hodgkin lymphoma patients do not respond to initial therapy or relapse within the first two years. There is a significant need to identify additional potential therapies in this patient population that may provide a more durable response and fewer incidences of relapse,” said Dirk Huebner, MD, Global Clinical Lead, Takeda Oncology.
Data previously presented at the ASH Annual Meeting in 2012 and 2014 from a phase 1 trial evaluating ADCETRIS plus AVD demonstrated that 24 of 25 patients (96 percent) achieved a complete remission. Long-term follow-up data demonstrated three-year overall survival was 100 percent and three-year failure-free survival was 92 percent. The most common adverse events of any grade occurring in more than 30 percent of patients were neutropenia, nausea, peripheral sensory neuropathy, fatigue, vomiting, diarrhea, insomnia, bone pain, constipation and hair loss.
ECHELON-1 Trial design
The randomized, open-label, phase 3 trial is investigating ADCETRIS+AVD versus ABVD as frontline therapy in patients with advanced classical HL. The primary endpoint is modified 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 and safety. The multi-center trial is being conducted in North America, Europe, South America, Australia, Asia and Africa. The study has enrolled approximately 1,300 patients who had histologically-confirmed diagnosis of Stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy. Data from the trial will be available when a pre-specified number of PFS events have occurred.