A Phase 2 Multicenter Trial of KTE-C19 (anti-CD19 CAR T Cells) in Patients With Chemorefractory Primary Mediastinal B-Cell Lymphoma (PMBCL) and Transformed Follicular Lymphoma (TFL): Interim Results From ZUMA-1

Background: ZUMA-1 is a phase 1-2 multicenter, open-label study evaluating the safety and efficacy of KTE-C19 in patients with refractory aggressive B-cell non-Hodgkin lymphoma. In phase 1, KTE-C19 demonstrated ongoing complete remissions with a tolerable safety profile (Neelapu, ASCO 2016). The phase 2 portion of the study has 2 cohorts based on tumor type: diffuse large B-cell lymphoma (cohort 1) or PMBCL/TFL (cohort 2). Results from cohort 2 at the time of the first pre-specified interim analysis of ZUMA-1 are presented here.

Methods: Patients received KTE-C19 at a target dose of 2 × 10⁶ (minimum 1 × 10⁶) anti-CD19 chimeric antigen receptor (CAR) T cells/kg after a low-dose conditioning chemotherapy regimen of cyclophosphamide (500 mg/m²) and fludarabine (30 mg/m²) daily for 3 days. The primary endpoint was overall remission rate per International Working Group criteria (Cheson, J Clin Oncol2007). Key secondary endpoints include duration of response, incidence of adverse events (AEs), levels of CAR T cells in the blood, and levels of serum cytokines. Key inclusion criteria include ≥ 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and chemorefractory disease defined as progressive disease or stable disease as best response to last line of therapy, or disease progression ≤12 months after autologous stem cell transplant. Patients must have received prior anti-CD20 therapy and an anthracycline-containing regimen.

Results: As of June 16, 2016, six patients in cohort 2 were treated with KTE-C19 and had at least 30 days of follow up. The median follow up time was 3.2 months. Fifty percent of patients had PMBCL and 50% had TFL. Median age was 55 years (range, 28-60), 67% were male, 67% ECOG performance status 0, and 50% were refractory to second or greater line of chemotherapy while 50% relapsed after autologous stem cell transplant. The objective response rate was 100%. All patients have ongoing complete remissions. Worst grades 3 and 4 treatment-emergent AEs occurred in 17% and 67% of patients, respectively. There were no grade 5 events. All grade 4 treatment-emergent AEs were cytopenias. KTE-C19-related worst grade 3 and 4 AEs occurred in 50% and 17% of patients, respectively. Patient incidence of any grade/grade 3/grade 4 CRS and neurotoxicity were 100%/0%/0% and 67%/33%/0%, respectively. All KTE-C19-related AEs have resolved. Biomarker endpoints will be presented.

Conclusions: KTE-C19 demonstrated early promising activity in patients with refractory PMBCL and TFL. The predominant toxicities of CRS and neurotoxicity were generally reversible. Updated trial results from 11 patients at interim analysis 2 will be presented. Clinical trial: NCT02348216.

This study is supported in part by funding from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program®