Upholding a recommendation made by the agency’s
Oncologic Drugs Advisory Committee in early August, the FDA has approved an
application by Seattle Genetics to use brentuximab vedotin in patients with
Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma.
On Aug. 10, ODAC voted unanimously to approve
brentuximab for use in patients with Hodgkin’s lymphoma after failure of
autologous stem cell transplant or after failure of at least two prior
multi-agent chemotherapy regimens in patients who were not candidates for ASCT.
The committee unanimously approved the drug for second-line therapy in patients
with systemic anaplastic large cell lymphoma the same day.
Brentuximab is an antibody-drug conjugate of an
anti-CD30 monoclonal antibody, and the cell-killing agent monomethyl auristatin
E. CD30 is a defining marker in Hodgkin’s lymphoma which is also expressed
FDA granted accelerated approval for the Hodgkin
lymphoma indication based on a single-arm, multicenter, clinical trial.
Patients who enrolled in the trial (n=102) had CD30-positive Hodgkin’s
lymphoma that relapsed after ASCT. The primary endpoint was ORR by independent
ORR=73% (95% CI, 65.0-83.0) with a median duration of
6.7 months (95% CI, 4.0-14.8) for patients assigned to brentuximab. The rate of
complete remission was 32% (95% CI, 23.3-42.3) with a median duration of 20.5
Accelerated approval for the systemic ALCL indication
was based on a single-arm, multicenter, clinical trial including 58 patients
who had CD30-positive systemic ALCL who had undergone front-line chemotherapy.
Again, primary endpoint was ORR by independent review facility.
ORR=86% (95% CI, 77.0-95.0) with a median duration of
12.6 months (95% CI: 5.7, NE). Complete remission rate was 57% (95% CI,
44.0-70.0) with a median duration of 13.2 months.
The most common adverse reactions in both trials were
neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper
respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough
and vomiting. Researchers observed serious adverse events in 31% of patients.