“By participating in the FDA’s Real-Time Oncology Review process and working closely with the FDA, we are now able to make the ADCETRIS regimen available to previously untreated patients with CD30-expressing PTCL in an unprecedented less than two weeks after submission of our supplemental BLA,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “TheECHELON-2 clinical trial demonstrated ADCETRIS plus CHP results in a superior outcome for patients when compared to current standard of care, CHOP. We want to thank the patients, physicians and their staff who participated in theECHELON-2 trial, which supported this FDA approval.”
TheECHELON-2 data will be presented at the American Society of Hematology (ASH) 2018 Annual Meeting, on Monday, December 3, 2018, at 6:15 pm PT at the San Diego Convention Center in Room 6F in San Diego, Calif. Patients inECHELON-2 were randomized to receive either a combination of ADCETRIS plus CHP or CHOP, a recognized standard of care for frontline PTCL. Results from the trial demonstrated that combination treatment with ADCETRIS plus CHP was superior to CHOP for progression free survival (PFS) as assessed by a Blinded Independent Central Review facility (BICR; hazard ratio=0.71; 95% CI, 0.54–0.93;p-value=0.011). This corresponds to a 29 percent reduction in the risk of progression, death, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease. The ADCETRIS plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; 95% CI,0.46-0.95;p-value=0.024). All other key secondary endpoints, including PFS in patients with sALCL (hazard ratio=0.59; 95% CI,0.42-0.84;p-value=0.003), complete remission rate (68% vs 56%;p-value=0.007) and objective response rate (83% vs 72%;p-value=0.003) were statistically significant in favor of the ADCETRIS plus CHP arm.
The safety profile of ADCETRIS plus CHP in theECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with AVD. The most common adverse events of any grade that occurred in at least 20 percent of patients in the ADCETRIS plus CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting and anemia. Serious adverse reactions occurring in at least two percent of ADCETRIS plusCHP-treated patients included febrile neutropenia, pneumonia, pyrexia and sepsis. Based onECHELON-2 clinical trial results, prophylactic growth factors(G-CSF) should be administered starting at cycle one for patients receiving ADCETRIS plus CHP for previously untreated PTCL.
ECHELON-2 Phase 3 Clinical Trial Design
The multi-center, 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 peripheralT-cell lymphoma, also known as matureT-cell lymphoma. The primary endpoint is progression-free survival (PFS) per BICR facility assessment, with events defined as progression, death due to any cause, or receipt of subsequent anticancer chemotherapy to treat 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 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. TheECHELON-2 trial was 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 seeImportant Safety Information, including Boxed Warning, at the end of this press release.