BLA Submitted to FDA for KTE-X19 as Treatment of Relapsed/Refractory MCL


A Biologics License Application for the investigational chimeric antigen receptor T-cell therapy agent, KTE-X19 has been submitted to the FDA for the treatment of adult patients with relapsed/refractory mantle cell lymphoma, according to a press release from Kite.<br /> &nbsp;


The BLA submission was prompted by positive data from the ZUMA-2 trial, which were presented recently at the American Society of Hematology (ASH) Annual Meeting. The data showed that an Independent Radiologic Review Committee (IRRC) assessed a 93% overall response rate (ORR), which included a 67% complete responses (CRs) in the study participants.1The investigator-assessed ORR was 86% (95% CI, 67% — 96%), with a CR of 57% (95% CI, 37% &ndash; 76%). At 12 months, KTE-X19 also demonstrated an 83% duration of response (DoR) (95% CI, 60% &ndash; 93%), a 71% progression-free survival (PFS) (95% CI, 50% &ndash; 84%), and an 86% overall survival (OS).2

Grade 3 and higher adverse events (AEs) occurred in 20% of the ZUMA-2 patients. The most common AEs were anemia (54%), platelet count decreased (39%), neutropenia (36%), neutrophil count decreased (32%), white blood cell count decreased (29%), encephalopathy (25%), and hypertension (21%). Grades 3 and 4 cytokine release syndrome (CRS) was also seen in 18% of patients and usually displayed as either hypotension (14%), hypoxia (14%), and pyrexia (11%). There were also cases of grade 3/4 neurologic events (NEs) observed in 46% of patients in the study. Theses NEs included encephalopathy (25%), confusional state (14%), and aphasia (11%). There were no grade 5 NEs or CRS incidences, and toxicities were reversible in most patients who did experience CRS or NEs.

CRS events began in a median of 2 days (range, 1 — 7) and were resolved by 13 days (range, 4 &ndash; 60). The median time to onset in patients who had NEs was 6 days (range, 1 &ndash; 15) and the median time to resolution was 20 days (range, 9 &ndash; 99). Grade 5 organizing pneumonia was reported in 1 patient, which was determined to be chemotherapy-related.

Participants had median CAR T cell levels of 99 cells/&micro;L (range, 0.4 — 2589) and 1542 cells/&micro;L (range, 5.5 &ndash; 27239), as measured by peak and the area below the curve. The peak CAR T cell expansions were examined between days 8 and 15 and gradually reduced over time.

&ldquo;There remains a significant need for new treatments for patients with relapsed/refractory MCL despite recent advances, so this regulatory filing is an especially important milestone for the MCL community,&rdquo; said Ken Takeshita, MD, global head of Clinical Development, Kite. &ldquo;We look forward to working with the FDA to bring KTE-X19 to appropriate patients as quickly as possible and continuing to deliver on the promise of our industry-leading cell therapy development program with a second CAR T therapy.&rdquo;

The ZUMA-2 trial is an ongoing single-arm study in which a chemotherapy regimen of fludarabine and cyclophosphamide is given to patients with relapsed/refractory MCL, followed by single infusion CAR transduced autologous T cells. The primary endpoint of the study is ORR, and the key secondary endpoints are DoR, best objective response, PFS, ORR, OS, and incidence of AEs.3

The study included patients who had up to 5 prior regimens for MCL, at least 1 measurable lesion, a platelet count of 75,000/uL, a creatinine clearance > 60mL/min, a cardiac ejection fraction &ge; 50%, and baseline oxygen saturation >92% on room air.

Patients with a known history of HIV, hepatitis B/C infection, seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, an autoimmune disease with central nervous system involvement, and presence of fungal, bacterial, or viral infection were excluded from the study.

KTE-X19 was previously granted an FDA Breakthrough Therapy Designation for MCL and a Priority Medicines stamp from the European Medicines Agency, both for the treatment of relapsed/refractory MCL. The drug is not approved in any country; however, it is being investigated in multiple clinical trials for the treatment of diseases like acute lymphoblastic leukemia and chronic lymphocytic leukemia.1

Kite reports that they also plan to submit Marketing Authorization Application for KTE-X19 in the European Union in early 2020.1


  1. Kite Sub Kite Submits Biologics License Application to U.S. Food and Drug Administration for Company&rsquo;s Second CAR T Cell Therapy [press release]. Santa Monica, California: Kite; December 11, 2019. Accessed December 12, 2019.
  2. Wang ML, Munoz J, Goy A, et al. KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) With Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 Study. Presented at: 2019 American Society of Hematology Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 754.
  3. A Phase 2 Multicenter Study Evaluating Subjects With Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2). Clinical Accessed December 12. 2019.
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