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The US Food and Drug Administration (FDA) has granted breakthrough designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL).
To create KTE-C19, T cells are modified to express a CAR designed to target CD19, a cell-surface protein expressed in B-cell lymphomas and leukemias.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The designation conveys all the features of the FDA’s fast track program, as well as more intensive FDA guidance on an efficient drug development program and eligibility for rolling review and priority review.
KTE-C19 research
In a study published in the Journal of Clinical Oncology last year, 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. One patient was lost to follow-up because of noncompliance, and 1 died soon after treatment. The researchers said the cause of death was likely cardiac arrhythmia.
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 chronic lymphocytic leukemia, 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 TFL (ZUMA-1), a phase 2 trial of relapsed/refractory mantle cell lymphoma (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult acute lymphoblastic leukemia (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric acute lymphoblastic leukemia (ZUMA-4).
Data from ZUMA-1 were presented at the 2015 ASH Annual Meeting (abstracts 2730 and 3991).
KTE-C19 is under development by Kite Pharma. 
The US Food and Drug Administration (FDA) has granted breakthrough designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL).
To create KTE-C19, T cells are modified to express a CAR designed to target CD19, a cell-surface protein expressed in B-cell lymphomas and leukemias.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The designation conveys all the features of the FDA’s fast track program, as well as more intensive FDA guidance on an efficient drug development program and eligibility for rolling review and priority review.
KTE-C19 research
In a study published in the Journal of Clinical Oncology last year, 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. One patient was lost to follow-up because of noncompliance, and 1 died soon after treatment. The researchers said the cause of death was likely cardiac arrhythmia.
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 chronic lymphocytic leukemia, 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 TFL (ZUMA-1), a phase 2 trial of relapsed/refractory mantle cell lymphoma (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult acute lymphoblastic leukemia (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric acute lymphoblastic leukemia (ZUMA-4).
Data from ZUMA-1 were presented at the 2015 ASH Annual Meeting (abstracts 2730 and 3991).
KTE-C19 is under development by Kite Pharma.
The US Food and Drug Administration (FDA) has granted breakthrough designation for the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 as a treatment for refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL).
To create KTE-C19, T cells are modified to express a CAR designed to target CD19, a cell-surface protein expressed in B-cell lymphomas and leukemias.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The designation conveys all the features of the FDA’s fast track program, as well as more intensive FDA guidance on an efficient drug development program and eligibility for rolling review and priority review.
KTE-C19 research
In a study published in the Journal of Clinical Oncology last year, 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. One patient was lost to follow-up because of noncompliance, and 1 died soon after treatment. The researchers said the cause of death was likely cardiac arrhythmia.
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 chronic lymphocytic leukemia, 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 TFL (ZUMA-1), a phase 2 trial of relapsed/refractory mantle cell lymphoma (ZUMA-2), a phase 1/2 trial of relapsed/refractory adult acute lymphoblastic leukemia (ZUMA-3), and a phase 1/2 trial of relapsed/refractory pediatric acute lymphoblastic leukemia (ZUMA-4).
Data from ZUMA-1 were presented at the 2015 ASH Annual Meeting (abstracts 2730 and 3991).
KTE-C19 is under development by Kite Pharma.