The European Medicines Agency (EMA) has validated and is now reviewing Kite Pharma’s application requesting the approval of its investigational chimeric antigen receptor (CAR) T-cell therapy KTE-X19 for adult patients with relapsed or refractory mantle cell lymphoma (MCL).
This submission follows a similar filing to the U.S. Food and Drug Administration (FDA) in December 2019.
“Relapse rates in mantle cell lymphoma remain overwhelmingly high and there is a significant need for new therapies that may improve patients’ prognosis,” Ken Takeshita, MD, Kite’s global head of clinical development, said in a press release.
“The EMA validation of our marketing application brings us closer to delivering on the promise of our industry-leading cell therapy development program, with the hope that we can bring KTE-X19 to appropriate patients in Europe as quickly as possible,” Takeshita added.
CAR T-cell therapy is a type of immunotherapy in which a patient’s T-cells — immune cells with anti-cancer activity — are collected and genetically modified in the lab to recognize specific cancer molecules. Once expanded to several million, the modified cells are infused back into the patient’s body, where they target and kill cancer cells.
KTE-X19 — developed by Kite, a subsidiary of Gilead Sciences — is an investigational CAR-T cell therapy designed to recognize CD19, a protein found on the surface of certain malignant B-cells.
The treatment shares the same design as the company’s Yescarta (axicabtagene ciloleucel, formerly known as KTE-C19), a CAR T-cell therapy approved in the U.S. and in Europe for adults with certain types of large B-cell lymphoma.
However, during KTE-X19’s manufacturing process, circulating tumor cells are separated from immune cells (a step called white blood cell enrichment), differentiating it from Yescarta. This step is necessary for certain types of B-cell blood cancers, including MCL.
KTE-X19’s marketing applications were supported by data from the ZUMA-2 Phase 2 trial (NCT02601313), which is evaluating the therapy’s safety and effectiveness in adults with relapsed or refractory MCL. Participants had received up to five prior therapies, including a chemotherapy, an anti-CD20 antibody, and a Bruton’s tyrosine kinase inhibitor (BTKi).
The trial’s primary goal is to assess objective response rate (ORR), or the combined rates of complete and partial responses. Secondary goals include duration of response, the time a patient lives without signs of disease progression, and overall survival, among others.
Results from the first 60 patients enrolled were recently presented at the 2019 American Society of Hematology Annual Meeting & Exposition, held in Orlando.
At a median follow-up of 12.3 months, the data showed that a single administration of KTE-X19 resulted in an ORR of 93%, including 67% of patients achieving a complete response.
These response rates were largely superior to those typically seen in MCL patients who progress on BTKi therapies (between 25% and 42%), according to a Targeted Oncology‘s news release.
At the time of the analysis, 78% of patients who achieved a complete response were still in remission. Also, 12 months after treatment, 83% of participants were still alive and 61% of them showed no signs of disease progression.
KTE-X19 showed a manageable safety profile, with fever (94%), low levels of a type of white blood cells (87%), low levels of platelets (74%), anemia (68%), and low blood pressure (51%) as the most frequent adverse events.
Severe or life-threatening adverse events included neurologic events (31%) and cytokine release syndrome (15%), a systemic inflammatory response that can be triggered by certain therapies. Two patients died due to adverse events, one with pneumonia not related to the CAR T-cell therapy, and one with a staphylococcus infection potentially related to KTE-X19.
Based on the positive trial data, KTE-X19 had been given the designations of priority medicines, or PRIME, from the EMA, and breakthrough therapy from the FDA as a potential treatment for adults with relapsed or refractory MCL. These designations are intended to accelerate KTE-X19’s development and review.
KTE-X19 is also being evaluated as a potential treatment for people with acute lymphoblastic leukemia and chronic lymphocytic leukemia in Phase 1/2 trials.
