Abstract CT135: Updated phase I results from ZUMA-1: a phase I-II multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with refractory aggressive non-Hodgkin lymphoma (NHL) (2016)

Abstract Introduction: Anti-CD19 CAR T cells with CD3 zeta and CD28 signaling domains showed durable remissions in subjects with relapsed/refractory advanced B cell malignancies at the NCI (Kochenderfer, JCO 2014). KTE-C19 utilizes the same CAR construct as investigated in the NCI study in a 6-8 day manufacturing process (Better, ASCO 2014). Updated results from the phase 1 portion of ZUMA-1 are presented here. Methods: Subjects received KTE-C19 at a target dose of 2 × 10⁁6 anti-CD19 CAR T cells/kg after a fixed dose conditioning chemo regimen of cyclophosphamide and fludarabine. The primary objective of phase 1 was to evaluate the safety of KTE-C19 as determined by the incidence of dose-limiting toxicities (DLT). Key secondary objectives were ORR, duration of response, and biomarkers. Key inclusion criteria were ? 18 years old, ECOG 0-1, and chemo-refractory disease defined as progressive disease or stable disease as best response to last line of therapy, or disease progression ? 12 months after ASCT. Results: As of 20 Nov 2015, 7 subjects were dosed. All subjects were evaluable for safety and 6 were evaluable for efficacy with a median follow up time of 13 weeks post KTE-C19 infusion. 1 subject experienced a DLT of grade (gr) 4 encephalopathy and gr 4 cytokine release syndrome (CRS) and died due to an intracranial hemorrhage deemed unrelated to KTE-C19 per the investigator. CRS and neurotoxicity were managed with supportive care, α-IL6R and steroids. 5 of 7 (71%) subjects responded including 4 CRs (57%). CAR T cells peaked within 2 weeks and were detectable 1-3+ months post infusion. Conclusions: The KTE-C19 regimen evaluated was safe for further study. The predominant toxicities include CRS and neurotoxicity which are generally reversible. CRs and PRs have been observed in subjects with refractory disease. The potentially pivotal phase 2 portion of the study is ongoing (NCT02348216). SubjectSex/Age/ECOGDisease TypeTreatment HistoryGr 3 or Higher KTE-C19-Related Adverse EventsBest Response1M/59/0DLBCLRelapse ≤ 12 mo after ASCTGr 3 encephalopathy (resolved)Partial Response (PR)3M/69/1DLBCLRefractory to 2nd line chemotherapyGr 3 tremor (resolved)Complete Remission* (CR)Gr 3 delirium (resolved)Gr 3 agitation (resolved)Gr 3 restlessness (resolved)Gr 3 somnolence (resolved)4M/69/0DLBCLRefractory to 4th line chemotherapyGr 3 encephalopathy (resolved)Stable DiseaseGr 3 hypophosphataemia (resolved)5M/67/1DLBCLRelapse ≤ 12 mo after ASCTNoneComplete RemissionOngoing 3 mo+6F/34/0DLBCLRelapse ≤ 12 mo after ASCTGr 3 hypoxia (resolved)Complete RemissionOngoing 3 mo+7M/40/0DLBCLRelapse ≤ 12 mo after ASCTNoneComplete RemissionOngoing 3 mo+8F/29/1DLBCLRefractory to 1st, 2nd, 3rd line chemotherapyGr 4 CRSNEGr 4 encephalopathy This study is supported in part by funding from The Leukemia &amp; Lymphoma Society (LLS) Therapy Acceleration Program® Citation Format: Armin Ghobadi, Frederick L. Locke, Sattva S. Neelapu, Tanya Siddiqi, Julio C. Chavez, Chitra M. Hosing, Nancy L. Bartlett, Lihua E. Budde, Adrian Bot, John M. Rossi, Marika Sherman, Lynn Navale, Meg Elias, Jeff Wiezorek, William Y. Go. Updated phase I results from ZUMA-1: a phase I-II multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with refractory aggressive non-Hodgkin lymphoma (NHL). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT135.