SANTA MONICA, Calif.– Kite, a Gilead Company (Nasdaq: GILD), announced today results from the primary analysis of ZUMA-3, a global, multicenter, single-arm, open-label Phase 1/2 study evaluating its chimeric antigen receptor (CAR) T-cell therapy Tecartus® (brexucabtagene autoleucel) in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). 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 2 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 ≥3 adverse events occurred in 95% of patients, with anemia (49%) and pyrexia (36%) most frequently reported. Grade ≥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 U.S. Food and Drug Administration (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 (≥18 years old) with relapsed or refractory ALL.
“The data presented at ASCO today validate the response rates seen in the Phase 1 portion of the ZUMA-3 study and the transformative potential of Tecartus in adult patients with ALL,” said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. “We have already seen the impact of Tecartus for patients with relapsed or refractory mantle cell lymphoma, and these new data are a significant next step in our continued commitment in developing our therapies for patients with leukemias and lymphomas.”
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; see below for Indication and Important Safety Information.
Tecartus has not been approved by any regulatory agency for the treatment of adult patients with relapsed or refractory ALL. Its safety and efficacy are currently under review by the FDA for this indication.