information: Presentation of results at a congress
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Kite Pharma (USA - CA)
Product: axicabtagene ciloleucel (KTE-C19) (autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3 zeta chimeric antigen receptor)
- cell therapy/immunotherapy product/gene therapy/CAR-T cell therapy. KTE-C19 is Kite Pharma's lead product candidate in which a patient's T cells are genetically modified using a gammaretroviral vector to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias.
Disease: acute lymphoblastic leukemia (ALL)
area: Cancer - Oncology
- ZUMA-3 is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). The objectives of the study are to evaluate the safety and efficacy of KTE-C19 in this patient population.(NCT02614066)
- • On December 11, 2017, Kite, a Gilead company, announced updated results from the ongoing Phase 1/2 ZUMA-3 study of KTE-C19, a CD19 chimeric antigen receptor T (CAR T) cell therapy, which is investigational for the treatment of adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL). With a minimum of eight weeks of follow-up, 71 percent of ALL patients (n=17/24) who received a single infusion of KTE-C19 achieved complete tumor remission (complete remission (CR) or CR with incomplete hematological recovery). The ZUMA-3 study results were presented in an oral session at the Annual Meeting of the American Society of Hematology (ASH) in Atlanta.
- At the time of data cutoff, 24 patients were evaluable for response. KTE-C19 demonstrated a 71 percent (n=17/24) rate of complete remission, with 100 percent of responders having no detectable minimal residual disease, including in those with high tumor burden and high risk genetic abnormalities. In the safety analysis of 29 patients, adverse events were consistent with the known toxicities of CD19 CAR T treatment, including Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities in 28 percent (n=8/29) and 52 percent of patients (n=15/29), respectively. Two patients receiving KTE-C19 died due to adverse events, including one patient with a cerebrovascular accident not related to KTE-C19 treatment approximately seven weeks after treatment and a previously reported patient who experienced fatal CRS.
• On June 5, 2017, Kite Pharma announced that 73 percent of patients achieved complete remission, including those with incomplete or partial recovery of bone marrow, in an updated analysis of the Phase 1 ZUMA-3 trial of KTE-C19 in adults with high burden relapsed/refractory acute lymphoblastic leukemia. All responders tested negative for minimal residual disease. In the Phase 1 trial, 11 patients were treated with KTE-C19 at two target dose levels (2.0×106/kg and 1.0x106/kg). No dose-limiting toxicities (DLT) occurred in the trial. Both doses were tolerable and responses were achieved at each level. Ongoing complete remissions have been observed at 2.0+ to 7.4+ months. Three of 11 (27 percent) patients had grade 3 or higher cytokine release syndrome (CRS) and six of 11 (55 percent) had grade 3 or higher neurologic events. These adverse events were generally reversible. As previously reported at ASH 2016, one patient experienced fatal CRS. In order to further improve the safety profile of KTE-C19, ZUMA-3 is also evaluating additional patients who will receive tocilizumab within 36 hours post-KTE-C19 infusion, and a lower dose of 0.5×106 CAR T cells/kg. Kite plans to initiate Phase 2 of the ZUMA-3 trial in 2017.
- • On December 5, 2016, Kite Pharma announced that 82 percent of patients (9 out of 11) achieved complete remission or complete remission with incomplete or partial hematological recovery in a preliminary analysis of the Phase 1 ZUMA-3 and ZUMA-4 trials of KTE-C19 in adult and pediatric relapsed/refractory acute lymphoblastic leukemia (r/r ALL). In these patients, 100 percent of responders tested negative for minimal residual disease (MRD), which has been shown to correlate with risk of disease relapse in ALL. The data were presented at the American Society of Hematology (ASH) Annual Meeting in San Diego.
- In the Phase 1 trials, 13 patients were treated with KTE-C19. Eleven patients were evaluable for response and two patients have not reached the evaluation time point at the data cutoff. Patients received a low-dose conditioning chemotherapy regimen based on extensive clinical experience at the National Cancer Institute (NCI).
- Five of 13 (38 percent) patients had ? grade 3 cytokine release syndrome (CRS) and five of 13 (38 percent) had ? grade 3 neurological events. One patient in ZUMA-3 died from KTE-C19 related CRS and one patient in ZUMA-4 died from a disseminated fungal infection unrelated to KTE-C19. No cerebral edema has been observed.
- KTE-C19 was successfully manufactured in these 13 patients across a range of absolute lymphocyte and blast counts in a centralized and streamlined process of six to eight days.