Results from the completed Phase I of the ZUMA-3 study, a single-arm, multicenter, registrational Phase I/II study evaluating KTE-X19 (Kite Pharma), an investigational CD19 chimeric antigen receptor T (CAR T) cell therapy for the treatment of adult patients (?18 years old) with acute lymphoblastic leukemia (ALL) whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation.
The objectives of the study was to evaluate the safety and efficacy of KTE-X19 in this patient population. The results of the clinical trial is expected to provide guidance on dosing and safety management for KTE-X19 to inform the ongoing Phase II study.
The investigational CD19 CAR T cell therapy, KTE-X19, has the same construct as axicabtagene ciloleucel (Yescarta? Kite Pharma). However, the manufacturing process for KTE-X19 differs from that of axicabtagene ciloleucel and includes the enrichment of lymphocytes. Lymphocyte enrichment is necessary in certain B-cell malignancies for which KTE-X19 in under investigation.
Acute lymphoblastic leukemia, one of the diseases for for which the drug is being studied, is an aggressive type of blood cancer which can also involve the lymph nodes, spleen, liver, central nervous system and other organs.
The latest, updated data was presented during an oral session during the annual meeting of the American Society of Clinical Oncology (ASCO) being held in Chicago, May 31 ? June 4, 2019 
By the end of Phase I, 45 patients received KTE-X19 at one of three different doses levels [2 x 106 cells/kg (n=6), 1 x 106 cells/kg (n=23), or 0.5 x 106 cells/kg (n=16)].
Patients enrolled in this study were primary refractory or relapsed/refractory after at least two prior lines of therapy. Of 41 patients who were evaluable for efficacy after a minimum two months of follow-up (median follow-up of 16 months), 68% achieved complete response (CR) or CR with incomplete hematological recovery (CRi) and 100% of responders had undetectable minimal residual disease (MRD). Of the 23 patients treated with the dose level that will be used in the ongoing Phase II study (1 x 106 cells/kg), 19 were evaluable for efficacy.
At the time of data cut-off (median duration of remission = 12.9 months), 16 (84%) patients achieved CR or CRi, and 12 patients (75%) were in ongoing response.
No dose-limiting toxicities (DLTs) were identified. Grade ?3 cytokine release syndrome (CRS) events and neurologic events occurred in 29 percent and 38 percent of all patients, respectively. As previously reported, two patients experienced KTE-X19?related Grade 5 adverse events (AEs) during the study; one developed stroke in the context of CRS and neurologic events, and one experienced multiorgan failure secondary to CRS.
Among patients receiving 1 x 106 cell/kg (n=23), 26% experienced Grade ?3 CRS, and 43% experienced Grade ?3 neurologic events.
A revised AE management protocol was implemented in nine patients treated with 1 x106 cells/kg of KTE-X19 during the study. In this revised protocol, corticosteroids were initiated at onset of Grade ?2 neurologic events (versus previous onset of Grade 3) and tocilizumab was only given for management of toxicities in the context of CRS (versus prophylactic administration in Cohort 2). Of those patients, two (22 percent) had Grade 3 CRS and one (11%) had Grade 3 neurologic events. There were no Grade 4/5 events.
?Adults with relapsed or refractory ALL represent an extremely difficult-to-treat patient population,? said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida.
?We?re encouraged by the high response rates in this study, as well as the reduced incidence and severity of CRS and neurologic events that were observed following implementation of the revised safety management protocol. We are now evaluating the use of KTE-X19 at the selected dose with this safety management protocol in the ongoing ZUMA-3 Phase 2 study,? Shah added.
?The completion of the Phase I portion of the ZUMA-3 trial is an important milestone for our second investigational CAR T cell therapy,? said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead, the parent company of Kite Pharma.
?We are pleased with the high response rates observed with KTE-X19 in this trial, and the progress of our broader effort aimed to further improve the benefit/risk profile of CAR T therapy through the investigation of novel safety management approaches,? McHutchison added.
KTE-X19 is an investigational therapy that has not been approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority for any uses. Efficacy and safety have not been established.
 Shah BD, Bishop MR, Oluwole OO, Logan A, Baer MR, Donnellan WB, Carr-O’Dwyer KM, et al. End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). J Clin Oncol 37, 2019 (suppl; abstr 7006) [Abstract]