Kite’s Investigational CAR-T Cell Therapy Shows Promise in Phase 1/2 Trial

A single infusion of KTE-X19, Kite Pharma‘s investigational CD19 CAR-T cell therapy, leads to high response rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL), Phase 1/2 trial data show.

The findings were presented during an oral session titled, “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),” at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Kite, which is now part of Gilead Sciences, is a biopharmaceutical company focused on the development of cancer immunotherapies. More specifically, CAR-T cell therapy, a type of immunotherapy in which researchers collect a patient’s T cells — immune cells with anti-cancer activity — and engineer them to recognize and eliminate cancer cells. The treated cells are then inserted back into the patient’s body to fight the tumor.

KTE-X19 is an investigational CD19 CAR-T cell therapy that shares the same construct as the company’s Yescarta (axicabtagene ciloleucel, formerly known as KTE-C19), a CAR-T cell therapy that has been approved by the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of adults with certain types of large B-cell lymphoma.

Despite sharing the same design, the manufacturing process of KTE-X19 differs slightly from that of Yescarta, because it includes a step of white blood cell enrichment, which is necessary for certain types of B-cell blood cancers, for which the compound is currently under investigation.

The safety and efficacy of KTE-X19 in adult patients with relapsed or refractory ALL who had received at least two prior therapies is being assessed in the multi-center, single-arm, ZUMA-3 Phase 1/2 (NCT02614066) trial.

Now Kite has announced data from the first phase of the study, which recently was completed. The company plans to use these findings as a guideline for treatment dosing and safety management for the trial’s ongoing second phase.

By the end of phase 1, 45 patients had already received one of three doses of modified T cells (500,000 cells, 1 million, or 2 million cells per kg body weight).

Among the 41 who were eligible for treatment efficacy assessments after a minimum follow-up period of two months, 68% had achieved a complete response (complete tumor eradication, CR) or CR with incomplete hematological recovery (CRi). All patients showed undetectable minimal residual disease (MRD; very low number of cancer cells remaining after treatment).

Of the 23 patients who received the intermediate dose of modified T cells (1 million cells/kg), which will also be used during the second phase of the study, 19 were eligible for efficacy assessments. At the time of data cutoff, 84% of the patients had achieved a CR or CRi to treatment and 75% were still responding to treatment. At that time, patients had been in remission for a median of 12.9 months.

Approximately a third of the patients participating in the study experienced severe or worse cytokine release syndrome (a systemic inflammatory response that can be triggered by certain drugs, CRS) (29%) and neurologic side effects (38%).

As in previous studies, two patients died because of adverse events related to KTE-X19: one suffered a stroke associated with CRS accompanied by neurologic complications; the other experienced multi-organ failure after developing CRS.

Among those receiving 1 million cells/kg, 26% had severe or worse CRS and 43% developed severe or worse neurologic side effects. These values decreased substantially in a sub-group of patients who were treated with a revised protocol (22% and 11%).

In the revised protocol, corticosteroids were administered immediately once patients showed signs of moderate (as opposed to severe) neurological side effects and tocilizumab was only initiated to control treatment toxicity when patients had already developed CRS (instead of being administered as a preventive measure).

“Adults with relapsed or refractory ALL represent an extremely difficult-to-treat patient population,” Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida, said in a press release.

“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 said.

“The completion of the Phase 1 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 at Gilead. “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.”

The abstract presented at the ASCO annual meeting has also been included in the 2019 Best of ASCO, an initiative that summarizes the most cutting-edge research presented during the meeting in a two-day-program. This year, the initiative will be held in Seattle (July 19 and 20), Austin (July 26 and 27) and Baltimore (Aug. 2 and 3).