PS945 KTE‐X19, AN ANTI‐CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: END OF PHASE 1 RESULTS OF ZUMA‐3

Background: KTE‐X19 is an autologous anti‐CD19 chimeric antigen receptor (CAR) T cell therapy under investigation for adult relapsed/refractory acute lymphoblastic leukemia. In an interim analysis of Phase 1 of ZUMA‐3 (NCT02614066), we reported manageable safety and encouraging efficacy of KTE‐X19; 72% of patients achieved a complete remission (CR) or CR with incomplete bone marrow recovery (CRi; Wierda et al, ASH 2018. #897). Aims: The aim of this report is to present end of Phase 1 results of ZUMA‐3. Methods: Adults with relapsed/refractory B cell acute lymphoblastic leukemia, greater than 5% bone marrow blasts, and an Eastern Cooperative Oncology Group performance status of 0–1 received 2 × 10 6 , 1 × 10 6 , or 0.5 × 10 6 KTE‐X19 cells/kg after conditioning chemotherapy. Revised adverse event (AE) management was implemented for additional patients in a 1 × 10 6 dose cohort: corticosteroids were given earlier at onset of Grade ≥ 2 neurologic events (NEs) and tocilizumab was used only for active toxicity. The primary endpoint was the rate of dose‐limiting toxicities (DLTs). Key additional endpoints were KTE‐X19 levels, incidence of AEs, minimal residual disease, and CR/CRi rate. Results: As of 9/27/18, 45 patients had received KTE‐X19, with a median follow‐up of 16 months. The median age was 46 years (range, 18–77 years); 30 patients (66%) had ≥ 3 prior therapies, and the median bone marrow blasts before conditioning chemotherapy was 70% (range, 0%–97%). Six, 23, and 16 patients received 2 × 10 6 , 1 × 10 6 , and 0.5 × 10 6 KTE‐X19 cells/kg, respectively. There were no DLTs in the DLT‐evaluable patients. The most common Grade ≥ 3 AEs were hypotension (38%), pyrexia (38%), and thrombocytopenia (31%). There were 2 previously reported KTE‐X19–related Grade 5 AEs of cerebral infarction and multiorgan failure, both in the context of cytokine release syndrome (CRS). Grade ≥ 3 CRS and NEs occurred in 13 (29%) and 17 (38%) patients, respectively. Of 41 patients with ≥ 2 months of follow‐up, 68% had CR/CRi, and 73% had undetectable minimal residual disease. Of 19 patients with ≥ 2 months of follow‐up treated with 1 × 10 6 KTE‐X19 cells/kg, 16 (84%) had a CR/CRi, and the median event‐free survival was 15 months. In 9 patients treated with 1 × 10 6 KTE‐X19 cells/kg who received revised AE management, 2 (22%) had Grade 3 CRS, and 1 (11%) had Grade 3 NE, with no Grade 4/5 events. Summary/Conclusion: KTE‐X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA‐3 is ongoing at the 1 × 10 6 dose with revised AE management.