The US Food and Drug Administration (FDA) has granted orphan drug designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for several hematologic malignancies.
This includes primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
KTE-C19 previously received orphan designation from the FDA for the treatment of diffuse large B-cell lymphoma (DLBCL).
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity.
KTE-C19 also has breakthrough therapy designation from the FDA as a treatment for DLBCL, PMBCL, and transformed FL.
About KTE-C19
KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR designed to target CD19. The product is being developed by Kite Pharma, Inc.
In a study published in the Journal of Clinical Oncology, researchers evaluated KTE-C19 in 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of KTE-C19. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. The overall response rate was 92%. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with DLBCL, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Three of the CRs were ongoing at the time of publication, with the duration ranging from 9 months to 22 months.
Of the 4 patients with CLL, 3 had a CR, and 1 had a PR. All 3 CRs were ongoing at the time of publication, with the duration ranging from 14 months to 23 months.
Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR. The duration of the CR was 11 months at the time of publication.
KTE-C19 elicited a number of adverse events, including fever, hypotension, delirium, and other neurologic toxicities. All but 2 patients experienced grade 3/4 adverse events.
Three patients developed unexpected neurologic abnormalities. One patient experienced aphasia and right-sided facial paresis. One patient developed aphasia, confusion, and severe, generalized myoclonus. And 1 patient had aphasia, confusion, hemifacial spasms, apraxia, and gait disturbances.
KTE-C19 is currently under investigation in a phase 2 trial of refractory DLBCL, PMBCL, and transformed FL (ZUMA-1), a phase 2 trial of relapsed/refractory MCL (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult ALL (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric ALL (ZUMA-4).
Results from ZUMA-1 were recently presented at the 2016 AACR Annual Meeting (abstract CT135).
