Kite, a Gilead Company announced updated, four-year overall survival (OS) data from the pivotal ZUMA-3 study evaluating the CAR T-cell therapy Tecartus® (brexucabtagene autoleucel) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The findings showed a median OS of 25.6 months and a four-year OS rate of 40% (95% CI, 28-52) in all treated patients with a safety profile consistent with that observed in the three-year analysis. The results were presented in a poster presentation (Abstract #6531) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

In the poster being presented, patients treated with the pivotal dose of Tecartus in the pooled analysis Phase 1 and 2 (n=78), the median follow-up time was 53.6 months (range 44.7-82.3) with 4-year minimum follow-up. Among all treated patients, the median OS was 25.6 months, and 47 months in patients with complete remission or complete remission with incomplete hematologic recovery (n=57), the primary endpoint. In patients <26 years (n=15), median OS (95% CI) was 23.2 months (9.0-NE) and was 26.0 months (15.9-NE) in patients =26 years (n=63), OS was a key secondary endpoint.

Median OS (95% CI) in patients with one prior therapy (n=15) was 60.4 months (7.6-NE) and was 25.4 months (15.9-47.0) in patients with =2 prior therapies (n=63). Medians for OS (95% CI) in patients with (n=38) and without (n=40) prior blinatumomab were 15.9 (8.3-26.0) and 60.4 months (18.6-NE), respectively (unbalanced patient characteristics and small numbers limit interpretation of these results). Median OS (95% CI) was 36.3 months (10.2-NE) in responders who went on to subsequent allogeneic stem cell transplant (n=14) and 60.4 months (23.2-NE) in those who did not (n=43).

No new adverse events or deaths occurred since the three-year analysis. Rates of infection were Grade =3 and higher in patients over 26 years and in patients with prior blinatumomab. ZUMA-3 is an ongoing international multicenter (US, Canada, Europe), single arm, open label, registrational Phase 1/2 study of Tecartus in adult patients (=18 years old) with ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation.

The primary endpoint is the rate of overall complete remission or complete remission with incomplete hematological recovery by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and alloSCT rate were assessed as secondary endpoints. ALL is an aggressive and rare type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs.

While 80% of ALL occurs in children, it represents a devastating disease in adults. In adults, B-cell precursor ALL is the most common form, accounting for 75% of cases. Survival rates in adults with R/R B-ALL are poor, with median OS at less than eight months .

Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide. Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL). This indication is approved under accelerated approval based on overall response rate and durability of response.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Neurologic Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus.

Neurologic events occurred in 87% (68/78) of patients with ALL, including = Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events.

Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death.

For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.

The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus. Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.