Tecartus demonstrates high response rate in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.- Kite/Gilead

 The data were simultaneously published in The Lancet and presented during an oral session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from June 4 – 8 (Abstract #7002). “Outcomes in adults with acute lymphoblastic leukemia are poor relative to what is observed in children, with less than half of people over 20 years of age expected to survive the illness. It is on this background that CAR T-cell therapy with brexucabtagene autoleucel was tested in adults with relapsed B-ALL in ZUMA-3,” said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida. “In this international, multicenter study, we observed a response rate of 71%. Importantly, the majority of these responses were associated with undetectable minimal residual disease.” In the pivotal Phase II portion of the trial, 71 patients with relapsed or refractory disease were enrolled. Among treated patients (n=55), 47% had received three or more prior therapies. At a median follow-up of 16.4 months, 71% of treated patients achieved a complete response (CR) or CR with incomplete hematological recovery (CRi) with 31% in ongoing response at data cut-off. 97% of those responders had deep molecular remission, with undetectable minimal residual disease (MRD), and median overall survival (OS) among all responders was not reached. Among 25 patients with prior blinatumomab treatment, the CR/CRi rate was 60%. Among all treated patients, median duration of response (DOR), relapse-free survival (RFS), and OS were 12.8 months, 11.6 months and 18.2 months, respectively. Grade greater than 3 adverse events occurred in 95% of patients, with anemia (49%) and pyrexia (36%) most frequently reported. Grade greater than 3 cytokine release syndrome (CRS) and neurologic events occurred in 24% and 25% of patients, respectively, and were generally reversed with treatment. Two Grade 5 treatment-related events occurred (one brain herniation and one case of septic shock). Based on these data, the FDA has accepted the supplemental Biologics License Application (sBLA) and granted Priority Review designation for Tecartus for the treatment of adult patients with relapsed or refractory B-cell precursor ALL, with a target action date under the Prescription Drug User Fee Act (PDUFA) of October 1, 2021. If approved, Tecartus would become the first and only CAR T-cell therapy approved for adults ( greater than 18 years old) with relapsed or refractory ALL. In 2016, Tecartus received Breakthrough Therapy Designation in recognition of the unmet medical need in adult patients with relapsed or refractory B-cell precursor ALL. Tecartus is currently approved for the treatment of relapsed or refractory mantle cell lymphoma, as the first and only CAR T-cell therapy to receive accelerated approval from the FDA in this indication. The Tecartus U.S. Prescribing Information has a Boxed Warning in its product label regarding the risks of cytokine release syndrome (CRS) and neurologic toxicities, and Tecartus is approved with a risk evaluation and mitigation strategy (REMS) due to these risks. About ZUMA-3 ; ZUMA-3 is an ongoing international multicenter, registrational Phase 1/II study in adult patients (?18 years old) with ALL whose disease is refractory to or has relapsed following first standard systemic therapy with remission of 12 months or less, after two or more lines of systemic therapy or after allogeneic stem cell transplantation. The objectives of the study are to evaluate the safety and efficacy of Tecartus in this patient population. See- "KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase II results of the single-arm, open-label, multicentre ZUMA-3 study"-Bijal D Shah, MD, Armin Ghobadi, MD, Olalekan O Oluwole, MD, Prof Nicolas Boissel, MD et al. Published:June 04, 2021DOI:https://doi.org/10.1016/S0140-6736(21)01222-8.- The Lancet.