943TiP - ZUMA-1: A phase 2 multi-center study evaluating anti-CD19 chimeric antigen receptor (CAR) T cells in patients with refractory aggressive non-Hodgki...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Lymphomas
Presenter Sattva Neelapu
Citation Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375
Authors S.S. Neelapu1, F.L. Locke2, N.L. Bartlett3, T. Siddiqi4, I. Braunschweig5, L.J. Lekakis6, A. Goy7, J. Castro8, O. Oluwole9, D. Miklos10, J. Timmerman11, C. Jacobson12, P.M. Reagan13, I. Flinn14, U. Farooq15, P. Stiff16, L. Navale17, M. Elias17, J. Wiezorek17, W.Y. Go17
  • 1Department Of Lymphoma/myeloma, The University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Department Of Blood And Marrow Transplantation, Moffitt Cancer Center, 33612 - Tampa/US
  • 3Siteman Cancer Center, Washington University School of Medicine, St. Louis/US
  • 4Department Of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte/US
  • 5Department Of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx/US
  • 6Sylvester Cancer Center, University of Miami, Miami/US
  • 7Clinical Divisions, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack/US
  • 8Moores Cancer Center, University of California San Diego, La Jolla/US
  • 9Hematology And Stem Cell Transplantation Section, Division Of Hematology/oncology, Department Of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville/US
  • 10Division Of Blood And Marrow Transplantation, Stanford University School of Medicine, Stanford/US
  • 11Division Of Hematology & Oncology, Department Of Medicine, And Department Of Pathology & Laboratory Medicine, University of California, Los Angeles/US
  • 12Department Of Medical Oncology, Dana-Farber Cancer Institute, Boston/US
  • 13Department Of Medicine, University of Rochester Medical Center, Rochester/US
  • 14Department Of Hematology & Oncology, Sarah Cannon Research Institute, Nashville/US
  • 15Division Of Hematology, Oncology And Blood And Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City/US
  • 16Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood/US
  • 17-, Kite Pharma, Santa Monica/US

Abstract

Background

Diffuse large B-cell Lymphoma (DLBCL) is 30%-58% of all NHL and has an incidence of 3.8/100,000 in Europe (Tilly et al, Ann Oncol 2015). KTE-C19 is an autologous anti-CD19 CAR T cell therapy with CD28/CD3&zgr; signaling domains centrally manufactured using a streamlined 6-8–day process (Better et al, ASCO 2014). The multicenter phase 1 portion of ZUMA-1 found that KTE-C19 was safe for further study in refractory, aggressive NHL. Toxicities include generally reversible cytokine release syndrome and neurotoxicity. The phase 1 overall response rate (ORR) was 71%; complete remission (CR) rate was 57% (Locke et al, ASH 2015). Here, we describe the enrolling phase 2 portion of ZUMA-1.

Trial design

Approximately 112 patients with refractory, aggressive NHL will be enrolled into cohort 1 (approximately 72 patients with DLBCL) or cohort 2 (approximately 40 patients with primary mediastinal large B cell lymphoma or transformed follicular lymphoma). Patients will receive a fixed dose of 30 mg/m2/day fludarabine and 500 mg/m2/day cyclophosphamide conditioning chemo (chemo) x 3 days followed by a single infusion of KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Eligible patients will have chemo-refractory disease (progressive disease [PD] or stable disease to most recent chemo or PD/recurrence ≤12 months of prior autologous stem cell transplant), ≥18 years old, ECOG PS 0-1, adequate marrow, renal, hepatic, and cardiac function, and prior anti-CD20 monoclonal antibody and an anthracycline-containing chemo regimen. Patients with prior CAR T cell or other genetically modified T cell therapy, clinically significant infection, or current or history of central nervous system lymphoma are ineligible. The primary objective is to evaluate KTE-C19 efficacy by ORR (CR + partial remission). Key secondary objectives include duration of response, progression-free survival, overall survival, safety, pharmacokinetics, pharmacodynamics, and predictive biomarker analyses. The study is planned at approximately 25 sites in the US and EU. Accrual began November 2, 2015.

Clinical trial identification

NCT02348216

Legal entity responsible for the study

Kite Pharma

Funding

Kite Pharma

Disclosure

S.S. Neelapu, U. Farooq: Research funding from Kite Pharma. F.L. Locke: Scientific advisory for Kite Pharma. N.L. Bartlett: Scientific advisory for Gilead. T. Siddiqi: Speaker's bureau for Pharmacyclics, Janssen, and Seattle Genetics. A. Goy: Honoraria, consultancy, speaker's bureau for Pharmacyclics and Johnson and Johnson; Honoraria and consultancy for Celgene, Takea, and Acerta; Consultancy for Infinity. D. Miklos: Research funding from Kite Pharma, Pharmacyclics, Janssen, Roche, Genentech, Novartis, Adaptive Biotechnology; scientific advisory for Pharmacyclics, Novartis, Seattle Genetics, and BMS; speaker's honoraria for Sanofi. I. Flinn: Research funding from Pharmacyclics and Janssen. L. Navale, J. Wiezorek, W.Y. Go: Employment with Kite Pharma. M. Elias: Employment from Kite Pharma. All other authors have declared no conflicts of interest.