Biopharmaceutical company Kite has announced long-term follow up results of two studies for its CAR T-cell therapy Tecartus (brexucabtagene autoleucel). The results of both a three- and two-year follow-up of the company’s ZUMA trial were announced at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
The announcement included the three-year follow-up of ZUMA-2, a Phase 2 global, multi-centre study evaluating the efficacy of brexucabtagene autoleucel in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), and two-year follow-up of ZUMA-3, a global, multi-centre, single-arm, open-label Phase 1/2 study evaluating the therapy in adult patients with R/R B-cell acute lymphoblastic leukaemia (B-ALL).
In 2020, Kite’s brexucabtagene became the first CAR-T cell therapy to be approved in Europe for adult patients with relapsed or refractory mantle cell lymphoma after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor.
In the ZUMA-2 trial, the overall response rate (ORR) to Tecartus was 91% with 68% of treated patients achieving a complete response (CR). The average overall survival for treated patients was a little under four years (46.6 months). However overall, those patients who achieved a CR have not reached the median OS. The average OS at 30 months was 60.3%.
Speaking about the trial, Michael Wang, MD, ZUMA-2 Lead Investigator and Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center said: “There remains a significant need among patients living with MCL for therapies that provide a long-term response, as many patients have high-risk disease that is more likely to relapse or progress following multiple lines of treatment. The three-year data from ZUMA-2 represent the longest follow-up for a CAR T-cell therapy in MCL patients to date and are impressive in their demonstration of brexu-cel to elicit durable long-term responses.”
For the ZUMA-3 trial, the majority of patients had been pre-treated at last two prior therapies, and 47% had received three or more prior therapies. At 29.7 months 73.1% of treated patients achieved a CR or CR with incomplete haematological recovery (CRi). The median OS was 25.4 months for both Phase 2 treated patients and pooled Phase 1 and 2 treated patients. For patients in the Phase II trial who received a CR, the median OS had not been reached at data cutoff.
“With two years of follow-up and an expanded data set in ZUMA-3 in a heavily pre-treated patient population, we’ve observed a high durable response rate, with the majority of the responses associated with undetectable minimal residual disease following treatment with brexu-cel,” said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida. “For adult patients with B-ALL, this is a marked improvement relative to historical standards of care, so these treatment results are particularly important.”
“We are very encouraged by the totality of these data, which suggest a significant and sustained response with brexucabtagene autoleucel for people living with difficult-to-treat blood cancers like MCL and B-ALL,” said Frank Neumann, MD, PhD, SVP & Global Head of Clinical Development, Kite. “These longer-term results add to the growing maturity of data on Kite’s CAR T-cell therapies.”
Whilst Kite states that no new safety signal was observed during the extended follow-up, there were a number of adverse events (AE) which occurred during the ZUMA-2 trial. The most frequent of which was neutropenia, a condition where you have a low number of white blood cells in your blood, causing the immune system to become weakened. Of these cases, 10% were life threatening.
In the ZUMA-3 cohort, a fatal Grade 5 AE has occurred since the trial’s primary analysis and was put down to graft-versus-host disease rather than being treatment related.