The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for the investigational PD-1 immune checkpoint inhibitor nivolumab to treat Hodgkin lymphoma (HL) in patients who have failed autologous stem cell transplant and treatment with brentuximab vedotin.
The FDA’s decision is based on data from a cohort of HL patients in an ongoing phase 1b study of patients with relapsed or refractory hematologic malignancies.
According to the FDA, breakthrough designation is intended to expedite the development and review of drugs for serious or life-threatening conditions.
For a treatment to receive this designation, there must be preliminary clinical evidence that demonstrates the drug may offer substantial improvement over currently available therapy on at least 1 clinically significant endpoint.
Nivolumab is an investigational agent that binds to the checkpoint receptor PD-1 expressed on activated T cells. Researchers are investigating whether, by blocking this pathway, nivolumab would enable the immune system to resume its ability to recognize, attack, and destroy cancer cells.
Nivolumab is under investigation in multiple tumor types as monotherapy or in combination with other therapies. There are 35 trials of the agent underway, in which more than 7000 patients have been enrolled.
The breakthrough designation for nivolumab in HL is based on results of a 2-part phase 1 study, which have not been made public.
The researchers planned to enroll 100 patients with relapsed or refractory hematologic malignancies on this study. For the dose-escalation portion, the team planned to treat successive cohorts of patients using a 6+3 escalation design.
Patients would receive 1 mg/kg or 3 mg/kg of intravenous nivolumab every 2 weeks (although the first dose would be followed by a 3-week evaluation period) for 2 years, with the potential for an additional year of therapy for patients who progress.
Then, the researchers would enroll 5 cohorts of 16 patients representing the following tumor sites: HL/primary mediastinal B-cell lymphoma, multiple myeloma, B-cell lymphoma, T-cell lymphoma, and chronic myelogenous leukemia.
These patients would receive nivolumab at the maximum-tolerated dose identified in the first part of the study.
A poster describing the study plan was presented at the 2013 ASCO Annual Meeting (abstract TPS3113). The study is funded by Bristol-Myers Squibb, the company developing nivolumab.
