1048O - Ongoing complete remissions in phase 1 of ZUMA-1: a phase 1-2 multi-center study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cel...

Date 07 October 2016
Event ESMO 2016 Congress
Session Immunotherapy of cancer
Topics Immunotherapy
Presenter Frederick Locke
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors F.L. Locke1, S.S. Neelapu2, N.L. Bartlett3, T. Siddiqi4, J.C. Chavez5, C.M. Hosing6, A. Cashen3, L.E. Budde4, M. Sherman7, J.M. Rossi7, L. Navale7, Y. Jiang7, J. Aycock7, M. Elias7, J. Wiezorek7, W.Y. Go7
  • 1Blood And Marrow Transplantation, Moffitt Cancer Center, 33612 - Tampa/US
  • 2Department Of Lymphoma And Myeloma, The University of Texas MD Anderson Cancer Center, Houston/US
  • 3Siteman Cancer Center, Washington University School of Medicine, St. Louis/US
  • 4Department Of Hematology And Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte/US
  • 5Department Of Malignant Hematology, Moffitt Cancer Center, Tampa/US
  • 6Department Of Stem Cell Transplantation And Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston/US
  • 7-, Kite Pharma, Santa Monica/US

Abstract

Background

Diffuse large B-cell Lymphoma is 30%-58% of all NHL with an incidence of 3.8/100,000 in Europe (Tilly et al, Ann Oncol 2015). Therapy with CD28/CD3&zgr; anti-CD19 CAR T cells led to durable remissions in patients with relapsed/refractory B cell malignancies at the NCI (Kochenderfer, J Clin Oncol 2015). KTE-C19 utilizes the same CAR construct as the NCI trial but centrally manufactured in a streamlined 6- to 8-day process. We present updated ZUMA-1 phase 1 study data.

Methods

Patients received KTE-C19 at a target dose of 2 × 106 anti-CD19 CAR T cells/kg after cyclophosphamide (500 mg/m2/day) and fludarabine (30 mg/m2/day) conditioning chemotherapy (Locke, ASH 2015). The primary objective was KTE-C19 safety. Secondary objectives included overall response rate (ORR), duration of response, and levels of blood CAR T cells and serum cytokines. Inclusion criteria were ECOG 0-1 and chemotherapy-refractory disease defined as progressive disease (PD) or stable disease as best response to last line of therapy, or PD ≤ 12 months after autologous stem cell transplant (ASCT).

Results

As of April 16, 2016, seven patients received KTE-C19. One patient had a dose-limiting toxicity (DLT) of grade 4 encephalopathy and cytokine release syndrome (CRS), and grade 5 intracranial hemorrhage unrelated to KTE-C19. Except for the patient with DLT, all grade ≥3 KTE-C19 related toxicity resolved. ORR was 71% (57% complete response [CR]). Three patients with PD within 6 months of ASCT have ongoing CR at 6-9+ months. CAR T cells peaked within two weeks and were detectable 1-6+ months post infusion. Updated results as of September 2016 including up to 1 year of follow up will be presented.

Conclusions

Ongoing CRs have been observed at 9+ months after a single KTE-C19 dose in patients with refractory aggressive NHL. CRS and neurotoxicity were self-limiting and generally reversible. The central manufacturing process and KTE-C19 regimen were deemed safe and feasible for further study. The ZUMA-1 phase 2 study (NCT02348216) is ongoing.

Clinical trial identification

NCT02348216

Legal entity responsible for the study

Kite Pharma

Funding

Kite Pharma

Disclosure

F.L. Locke: Scientific advisory board for Kite Pharma. S.S. Neelapu: Research funding from Kite Pharma. N.L. Bartlett: Consultancy for Gilead. T. Siddiqi: Speaker's bureau for Pharmacyclics, Janssen, and Seattle Genetics. A. Cashen: Speaker's bureau for Seattle Genetics, Gilead, Novartis, and Spectrum. M. Sherman, J.M. Rossi, L. Navale, Y. Jiang, J. Aycock, M. Elias, J. Wiezorek, W.Y. Go: Employment with Kite Pharma. All other authors have declared no conflicts of interest.