Of 55 evaluable patients in ZUMA-3, 71% achieved complete remission (CR) or CR with incomplete hematological recovery (CRi).
Kite’s brexucabtagene autoleucel (KTE-X19; Tecartus), a CD19-directed autologous chimeric antigen receptor T-cell (CAR-T) therapy, has been granted marketing authorization by the European Commission (EC) for the treatment of patients aged 26 years and older with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL).
The authorization was supported by data from the phase 1/2 ZUMA-3 clinical trial (NCT02614066). Of the 55 evaluable patients in the study, 71% achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) at a median follow-up of 26.8 months. The median overall survival (OS) was 25.4 months in an extended data set that included all 78 pivotal dosed patients and was 47 months for patients who achieved CR or CRi. The median duration of remission (DOR) for efficacy-evaluable patients was 18.6 months.
“This approval makes Tecartus the first and only CAR T-cell therapy indicated for this population of patients, addressing a significant unmet medical need,” Christi Shaw, chief executive officer, Kite, said in a statement regarding the news. "This is also the fourth indication in Europe for which a Kite cell therapy is approved, clearly demonstrating the benefits they offer to patients, especially those with limited treatment options.”
In terms of safety, results in the ZUMA-3 trial for the 100 patients treated at the target dose were consistent with the previously established safety profile of Tecartus. Twenty-five percent of patients experienced grade 3 or higher cytokine release syndrome (CRS) and 32% of patients experienced grade 3 or higher neurologic adverse events (AEs); however, these were well-managed. Tecartus had previously been approved by the FDA and EC for adult patients with r/r mantle cell lymphoma (MCL) in 2020. The approvals were based on results of the phase 2 ZUMA-2 trial (NCT02601313). Tecartus was also previously approved by the FDA for the treatment of r/r B-cell ALL in the United States in 2021.
The ZUMA-3 trial, an on-going multicenter, open-label study, recruited patients aged 18 years and older who had been diagnosed with r/r B-cell precursor ALL. Participants were required to have morphological disease in the bone marrow, an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, and adequate renal, hepatic, pulmonary, and cardiac function according to pre-defined criteria. Patients previously treated with blinatumomab were additionally required to have CD19 tumor expression in the bone marrow or peripheral blood. Patients with Burkitt's leukemia/lymphoma, chronic myelogenous leukemia lymphoid blast crisis, isolated extramedullary disease, or central nervous system (CNS) abnormalities were excluded from the study. Patients with a history of malignancy other than non-melanoma skin cancer or carcinoma in situ were also excluded unless disease-free for at least 3 years. Patients with a primary immunodeficiency, an uncontrolled infection, or a history of a concomitant genetic syndrome were excluded as well. Other exclusion criteria were related to HIV and hepatitis, clinically significant cardiac disease, symptomatic deep vein thrombosis and pulmonary embolism, and other patient disease history or prior treatment history.
Participants received Tecartus intravenously, after a preconditioning regimen of chemotherapy that included intravenous administration of fludarabine and cyclophosphamide. The study’s primary end points are the percentage of patients who experienced dose limiting toxicities and the overall complete remission rate, defined as the percentage of participants achieving either CR or CRi. Secondary end points include minimum residual disease negative remission rate, CR rate per independent review, CRi rate per independent review, duration of remission per independent review, OS, relapse-free survival, and the percentage of participants experiencing treatment emergent AEs.
“Adults with relapsed or refractory ALL often undergo multiple treatments including chemotherapy, targeted therapy and stem cell transplant, creating a significant burden on a patient’s quality of life,” Max S. Topp, MD, professor and head of Hematology, University Hospital of Wuerzburg, Germany, added to the statement. “Patients in Europe now have a meaningful advancement in treatment. Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care.”
The ZUMA-2 trial recruited patients at locations in the United States, Canada, and Europe, and met its primary completion date on September 9, 2020. The study is expected to continue long-term follow-up until November 2034.