415TiP - ZUMA-3: A phase 1/2 multi-center study evaluation the safety and efficacy of KTE-C19 anti-CD19 CAR T cells in adult patients with relapsed/refracto...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Drug Development
Presenter Bijal Shah
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors B. Shah1, J. Castro2, N. Gökbuget3, M. José Kersten4, T. Hagenbeek4, W. Wierda5, G. Schiller6, A. Bot7, J.M. Rossi7, Y. Jiang7, L. Navale7, S. Stout7, J. Aycock7, J. Wiezorek7, R. Jain7
  • 1Department Of Hematological Malignancies, H. Lee Moffitt Cancer Center and Research Institute, 33612 - Tampa/US
  • 2Department Of Medicine And Moores Cancer Center, University of California San Diego, La Jolla/US
  • 3Department Of Medicine Ii, Goethe University Frankfurt, Frankfurt/DE
  • 4Department Of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam/NL
  • 5Department Of Leukemia, The University of Texas MD Anderson Cancer Center, Houston/US
  • 6N/a, UCLA Center for Health Sciences, Los Angeles/US
  • 7-, Kite Pharma, Santa Monica/US

Abstract

Background

ALL has an incidence of 1.2 to 1.4 per 100,000 per year in Europe (Saltman, BMC Cancer 2015). Although 75%-90% of adult patients with ALL achieve complete remission (CR) following initial treatment, eventually most relapse. R/R ALL has a poor prognosis, with a median survival of 4-8 months (Hoelzer, Ann Oncol 2016). Ongoing studies at the National Cancer Institute (NCI) using anti-CD19 CAR T cells with CD28/CD3&zgr; signaling domains showed durable remissions in pediatric patients with R/R ALL and adults with R/R B cell malignancies (Lee, Lancet 2015; Kochenderfer, J Clin Oncol 2015). KTE-C19 is an autologous, anti-CD19 CAR T cell therapy that uses the same construct as the NCI studies, manufactured in a streamlined 6- to 8-day process. Here, we describe a phase 1/2 study evaluating KTE-C19 in adult patients with R/R ALL.

Trial design

The primary objective is to evaluate efficacy of KTE-C19, assessed by overall CR rate (CR + CR with partial hematologic recovery). Key secondary objectives include duration of response, minimal residual disease-free rate, allogeneic stem cell transplant rate, OS, and safety. Exploratory objectives include pharmacokinetics, pharmacodynamics, and predictive biomarker analyses. Patients with R/R ALL will be treated with fixed-dose fludarabine and cyclophosphamide conditioning chemotherapy followed by a single infusion of KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Phase 1 will enroll 3-12 patients with the primary objective to evaluate the safety of KTE-C19. In phase 2, approximately 50 patients will be enrolled. Eligible patients will be ≥18 years with ≥5% marrow blasts, ECOG PS 0-1, and adequate bone marrow, renal, hepatic, and cardiac function. Patients with Ph+ ALL and low-burden central nervous system disease are eligible. Patients with Burkitt lymphoma or chronic myeloid leukemia in blast crisis, extramedullary disease only, active graft-versus-host disease, or clinically significant infection are not eligible. Accrual began in December 2015. The study is planned at approximately 25 sites in the US and EU. Clinical trial information: NCT02614066.

Clinical trial identification

NCT02614066

Legal entity responsible for the study

Kite Pharma

Funding

Kite Pharma

Disclosure

B. Shah: Advisory Board, Speaker Fees, Honorarium: Celgene; Honorarium: Bayer, Plexus Communications and Baxalta; Speaker Fees: Spectrum and Pharmacyclics; Research Funding: Rosetta Genomics; Advisory Board: Acetilon and Pfizer. W. Wierda: GSK research, Celgene consulting. G. Schiller: Research Funding: Novartis, Karyopharm, Astellas, Spectrum, Bluebird, Array Pharmaceutical; Honoraria, Research Funding, Speakers Bureau: Amgen and Celgene; Honoraria, Research Funding: Sunesis. A. Bot, J.M. Rossi, Y. Jiang, L. Navale, S. Stout, J. Aycock, J. Wiezorek, R. Jain: Employment with Kite Pharma. All other authors have declared no conflicts of interest.