The FDA Oncologic Drugs Advisory Committee (ODAC) unanimously recommended accelerated approval for the intravenous agent brentuximab vedotin (Adcetris), a CD30-direct antibody-drug conjugate (ADC), in 2 types of lymphoma.
The recommendations were based on the results of 2 single-arm phase II studies, SG035-0003, treating patients with relapsed or refractory Hodgkin lymphoma with previously received autologous stem cell transplant (ASCT), and SGO35-0004, examining anaplastic large cell lymphoma (ALCL), a rare, aggressive type of T-cell non-Hodgkin lymphoma.
"If approved, Adcetris would be the first in a new class of ADCs, utilizing stable linkers and potent cytotoxic payloads,” said Clay B. Siegall, PhD, president and chief executive officer of Seattle Genetics.
Patients in both trials received 1.8 mg/kg every 3 weeks for a maximum of 16 cycles. The primary endpoints of the studies were objective response rate (ORR), and the key secondary endpoints were duration of response and complete remission (CR) rate.
A single-arm study does not allow for attribution of adverse effects or for the use of time-of-event endpoints such as progression free survival and overall survival.
The SG035-0003 trial experienced an ORR in the 102 patients enrolled of 73% with a median duration of 6.7 months. The CR rate was 32% with a median duration of 20.5 months. ORR was 86% with a median duration of 12.6 months in the 58 patients recruited to the SGO35-0004 trial and CR was 57% with a 13.2 month median duration.
Observations of the 2 studies showed similar patterns in adverse events. Major safety issues included myelosuppression, infections, infusion reactions, and Stevens Johnson syndrome, an often life-threatening skin condition. The most severe side effects were peripheral sensory neuropathy, which occurred in 49% of patients with grade 3/4 events occurring in 9%, and neutropenia in 21% of patients with grade 3/4 events in 20% of patients.
More than 8800 cases of Hodgkin lymphoma are projected to be diagnosed in the United States in 2011; of these patients nearly 30% are relapsed or refractory, according to the American Cancer Society.