A taste of one’s own medicine

SANTA MONICA, Calif.—Clinical-stage biopharmaceutical company Kite Pharma Inc. announced clinical biomarker data from patients involved in an ongoing Phase 1 clinical trial of the company’s anti-CD19 chimeric antigen receptor (CAR) T cell therapy in June 2015. The company presented the data in a poster presentation at the 51^st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The presentation shared results from an ongoing Phase 1 clinical trial at the National Cancer Institute (NCI), being conducted under a Cooperative Research and Development Agreement (CRADA) between Kite Pharma and the NCI.

During the study, patients with various relapsed or refractory B cell malignancies, including non-Hodgkin’s lymphoma and chronic lymphocytic leukemia, received treatments of their own T cells genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B cell tumors. To create the anti-CD19 cells, patients underwent leukapheresis to obtain white blood cells that were then grown in the laboratory and genetically modified to attack only the tumor cells. These patients received conditioning chemotherapy with cyclophosphamide and fludarabine prior to beginning T cell therapy, a procedure designed to induce molecules that favor the homeostatic expansion, activation and trafficking of T cells in the body. Finally, the modified T cells were intravenously reintroduced to the patients.

Although the research team shared preliminary results at last year’s ASCO meeting showing 76 percent of evaluable patients (N=29) achieved an overall response rate, this year’s presentation included an updated analysis of a broad range of biomarkers that allowed researchers to draw additional conclusions.

According to the company’s ASCO meeting poster, titled “Biomarker Analysis of Patients Treated with Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cells,” the researchers concluded that anti-CD19 CD28zeta CAR T cells appear to be clinically effective, and noted the induction of durable responses in patients with both lymphoma and leukemia. The results of the study showed that the conditioning chemotherapy was associated with a significant rise in homeostatic cytokines and chemokines, which is consistent with the desired environment this conditioning was intended to produce.

The researchers further concluded that durable responses were possible without the CAR T cells remaining in circulation long after treatment, noting the CAR T cells frequently cleared from the blood and allowed normal B cell recovery to occur in the patients who experienced durable responses. Recovery of B cells occurred in seven of 12 patients with ongoing responses lasting more than 12 months.

In addition to gauging the therapy’s efficacy, the study also evaluated various T cell product characteristics. After assessing the results of the study, the research team concluded that a shorter manufacturing process yields CAR T cell products with a higher representation of naïve and central memory T cells, according to the presentation poster. Post-infusion, the CAR T cells showed a diversified subset composition of mainly differentiated T cells with some central memory or naïve T cells.

“The results being reported at ASCO provide additional key insights and further deepen our understanding of CAR T cell therapy,” according to Kite Pharma’s chief medical officer and executive vice president of research and development, Dr. David Chang. “We will continue to investigate biomarkers that may predict the clinical outcome in our ongoing KTE-C19 (anti-CD19 CAR T) clinical program,” which initiated patient dosing last month.” Chang was one of the authors on the poster presented at ASCO.

The ongoing clinical trial is currently recruiting participants, up to an estimated enrollment of 60, according to the National Institutes of Health Clinical Center. Eligibility includes adults aged 18 to 68 with B cell lymphomas or leukemias expressing the CD19 molecule. Patients will return to the clinic for a physical exam, review of side effects, lab tests and scans every one to three months for the first year after treatment, and then every six months to one year as long as their tumors continue to shrink. Follow-up visits take up to two days. Final data collection to complete the study is scheduled to take place in 2019.

Kite Pharma is a clinical-stage biopharmaceutical company primarily focused on engineered autologous T cell therapy designed to restore the immune system’s ability to recognize and eradicate tumors. Its pipeline includes a suite of chimeric antigen receptor and T cell receptor products at various stages of development.