Tecartus Shows Overall Survival Benefit for R/R B-ALL in 3-Year Follow-up Data

Kite’s brexucabtagene autoleucel (brexu-cel; KTE-X19; Tecartus), a CD19-directed autologous chimeric antigen receptor T-cell (CAR-T) therapy, provided an overall survival benefit to patients with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (B-ALL) in 3-year follow-up data from the phase 1/2 ZUMA-3 clinical trial (NCT02614066) presented at the 5th European CAR T-cell Meeting, taking place February 9-11, 2023, in Rotterdam, the Netherlands.¹

Among the 55 patients treated in the study’s phase 2 cohort, which dosed participants with 1x10⁶ CAR-T cells/kg, follow-up ranged from 32.7 to 44.6 months (median, 38.8). For this group, the median overall survival (OS) was 26 months, with an OS rate of 47.1% at 36 months (95% CI, 32.7-60.2). The overall complete remission (CR) rate was 71%, the CR with incomplete hematologic recovery (CRi) rate was 56%, and the subsequent allogeneic stem cell transplant (alloSCT) rate was 20%. It was noted that these 3 rates had not changed since the previous data analysis. The median OS for the 39 patients who had achieved CR or CRi was 38.9 months. Relapse-free survival (RFS) ranged from 2.7 to 20.5 months (median, 11.6) when censored at subsequent alloSCT and from 2.8 to 20.5 months (median, 11.7) when not censored at subsequent alloSCT (95% CI).

Among all 78 participants across the study’s phase 1 and phase 2 cohorts who received the 1x10⁶ CAR-T cells/kg dose, follow-up ranged from 32.7 to 70.3 months (median, 41.6). For this group, duration of response (DOR) ranged from 9.6 to 24.1 months (median, 18.6) when censored at subsequent alloSCT and from 10.3 to 24.1 months (median, 20.0) when not censored at subsequent alloSCT (95% CI). The median RFS in this cohort was 11.7 months (range, 6.1 to 20.5) regardless of censoring (95% CI). The median OS was 25.6 months (95% CI, 16.2-47.0), with 28 patients (36%) remaining alive as of the data cutoff. In terms of safety, the proportion of patients who experienced treatment-related adverse events (AEs) in the pooled 1x10⁶ CAR-T cells/kg dose cohorts did not differ from the previous data analysis and no new grade 5 AEs were observed. Patients in this group had a median of 2 prior therapies, with 47% having received at least 3 prior therapies.

“We are encouraged by the sustained benefit that a single one-time treatment of Tecartus continues to provide for patients living with this difficult-to-treat blood cancer,” Frank Neumann, MD, PhD, SVP, global head of Clinical Development, Kite, said in a statement regarding the news.¹ “Our hope is that these results, along with our commitment to long-term research of Tecartus, will continue to provide clarity to physicians on optimal treatment methods for these patients living with this rare disease who have suffered historically poor outcomes.”

Tecartus originally received approval from the FDA for the treatment of adult patients with B-ALL in October of 2021.² Nearly a year later, in September 2022, the European Commission approved Tecartus for patients aged 26 years and older with B-ALL.³ In both jurisdictions, Tecartus was the first CAR-T approved for the indicated patient populations.^2,3 The approvals were based on earlier results from the ZUMA-3 trial. Tecartus was also approved by the FDA for the treatment of adult patients with r/r mantle cell lymphoma in July 2020.⁴ A separate phase 1/2 clinical trial, ZUMA-4 (NCT02625480), is currently evaluating Tecartus for the treatment of pediatric patients with r/r B-ALL.

“For adult patients living with ALL, there is a need for therapeutic options that provide long-term responses,” Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida, added to the statement.¹ “The continued durable response and significant improvement in survival indicated by these new data can potentially establish a new standard of care for adult patients living with this aggressive form of leukemia.”

REFERENCES

1. Kite’s Tecartus CAR T-cell therapy demonstrates overall survival benefit in three-year follow-up of pivotal ZUMA-3 trial in relapsed/refractory B-cell acute lymphoblastic leukemia. News release. Kite, a Gilead Company. February 9, 2023. Accessed February 9, 2023. https://wwwam10.kitepharma.com/news/press-releases/2023/2/kites-tecartus-car-t-cell-therapy-demonstrates-overall-survival-benefit-in-three-year-follow-up-of-pivotal-zuma-3-trial-in-relapsedrefractory-b-cel 

2. U.S. FDA approves Kite’s Tecartus® as the first and only CAR T for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Kite. News release. Published October 1, 2021. Accessed October 1, 2021. https://bwnews.pr/3iq0Chg.

3. Kite’s CAR T-cell therapy Tecartus® granted European marketing authorization for the treatment of relapsed or refractory acute lymphoblastic leukemia (r/r all). News release. Kite. September 6, 2022. https://www.kitepharma.com/news/press-releases/2022/9/kites-car-t-cell-therapy-tecartus-granted-european-marketing-authorization-for-the-treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia 

4. U.S. FDA approves Kite’s Tecartus, the first and only CAR T treatment for relapsed or refractory mantle cell lymphoma. News Release. Published July 24, 2020. Accessed July 25, 2020. https://bit.ly/2ZVy6v9