The U.S. Food and Drug Administration (FDA) approved Seattle Genetics‘ application requesting that Adcetris (brentuximab vedotin) be used in combination with chemotherapy as a first-line treatment for systemic anaplastic large cell lymphoma (sALCL), a subtype of peripheral T-cell lymphomas (PTCL). The approval came less than two weeks after the application’s submission.
The approval — which is also for other PTCL patients whose tumors are positive for the CD30 factor, including angioimmunoblastic T-cell lymphoma, and PTCL not otherwise specified — came a day after the FDA granted Adcetris Breakthrough Therapy Designation for the same indication.
The decisions follow positive data from the ECHELON-2 Phase 3 trial (NCT01777152), where a combination of Adcetris plus CHP chemotherapy — cyclophosphamide, doxorubicin, and prednisone — reduced the risk of death by 34%, compared to CHOP chemotherapy —cyclophosphamide, doxorubicin, vincristine, and prednisone — alone.
“The ECHELON-2 clinical trial demonstrated Adcetris plus CHP results in a superior outcome for patients when compared to current standard of care, CHOP,” Clay Siegall, PhD, president and chief executive officer of Seattle Genetics, said in a press release. “We want to thank the patients, physicians and their staff who participated in the ECHELON-2 trial, which supported this FDA approval.”
Adcetris is an antibody-drug conjugate that targets the CD30 protein, located at the surface of many lymphomas, including some PTCL subsets. Once bound to CD30-positive cells, the antibody triggers the release of a toxic compound that causes cells to die.
ECHELON-2 included 452 patients with newly diagnosed PTCL whose tumors were positive for the CD30 factor. Of them, 75% had sALCL. Its main goal was to determine whether Adcetris add-on treatment could extend the time to disease progression or death compared to the standard CHOP chemotherapy.
The trial met its primary endpoint, with the Adcetris combination reducing the risk of disease progression by 29%. But other key secondary measures were also met.
Indeed, more patients responded to the combination than to CHOP — 83% to 72% — and achieved complete responses — 68% to 56%. Patients receiving Adcetris also had a 34% lower risk of death, and those with sALCL experienced a 41% reduction in their risk of disease progression or death.
The safety profile of Adcetris and CHP was similar to that of CHOP, and consistent with prior studies examining a combination of Adcetris with chemotherapy. The most common adverse events included peripheral neuropathy — a feeling of numbness in the hands and feet — nausea, diarrhea, low levels of white blood cells, fatigue, fever, and anemia.
“The current standard of care for initial treatment of peripheral T-cell lymphoma is multi-agent chemotherapy. That treatment has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments,” said Steven Horwitz, MD, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York.
“The ECHELON-2 clinical trial demonstrated Adcetris plus CHP was superior to the current standard of care, CHOP, for both progression-free survival and all other key secondary endpoints, including, most importantly, overall survival,” Horwitz said. “With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated.”
The FDA reviewed Adcetris under its Real-Time Oncology Review Pilot Program, which aims to accelerate the review process of safe and effective treatments, making them available for patients as early as possible, without compromising review quality.
The full data of the ECHELON-2 trial will be presented at the American Society of Hematology (ASH) 2018 Annual Meeting, Dec. 1-4 in San Diego, California. The presentation is titled “The ECHELON-2 Trial: Results of a Randomized, Double-Blind, Active-Controlled Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas.”