Frederick L. Locke, MD
The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (KTE-C19) has shown very promising results in patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal lymphoma, and transformed follicular lymphoma. The findings were recently presented at the 2017 AACR Annual Meeting.
In the 101 patients enrolled on the ZUMA-1 trial, results showed that the objective response rate (ORR) was 82%, including a complete response (CR) rate of 54%. In the intent-to-treat population, the 6-month overall survival (OS) rate was 80%. Moreover, the ZUMA-1 findings have been submitted to the FDA to support a biologics license application for axicabtagene ciloleucel as a treatment for transplant-ineligible patients with relapsed or refractory aggressive non–Hodgkin lymphoma.
“The results of this clinical trial are really exciting to us,” said lead study author Frederick L. Locke, MD. “We have seen that 82% of patients can have a response to this single infusion; 54% of patients can have a CR, and 44% of patients are in an ongoing response at the time of the data cutoff. Perhaps, most interestingly, is that the 6-month OS rate on the ZUMA-1 study was 80%, which compares very favorably to the historical SCHOLAR-1 control with standard-of-care therapy, where the 6-month OS rate was 55%, suggesting that this therapy—a single infusion of CAR T cells—can positively impact overall survival.”
In an interview with OncLive
during the AACR meeting, Locke, a medical oncologist at Moffitt Cancer Center, discussed the ZUMA-1 trial and the next steps going forward.
OncLive: Please provide an overview of the primary ZUMA-1 analysis being presented here at the 2017 AACR Annual Meeting.
We're here at the 2017 AACR Annual Meeting to present the primary analysis of the ZUMA-1 clinical trial that includes both the clinical results and biomarker analyses—to look at biomarkers that correlate to toxicity or predict for efficacy.
The clinical trial enrolls patients with DLBCL, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma, who are truly chemorefractory to their last line of therapy, meaning they had no response to their last line of therapy or relapsed within 12 months of an autologous transplant.
Can you provide background to this study?
The primary endpoint of the clinical trial was to evaluate the ORR, with 1 treatment of CAR T cells called axicabtagene ciloleucel (Kite Pharma), which is formally called KTE-C19. Patients are to receive fludarabine, cytotoxic conditioning chemotherapy, and 1 single infusion of anti-CD19 CAR T cells of axicabtagene ciloleucel. The primary endpoint was to look at the response rate after this treatment, compared with a robust historical control called SCHOLAR-1, which is a more than 600-patient international meta-analysis looking at that same patient population with standard-of-care therapy. There were 111 patients enrolled on the clinical trial. Ninety-nine percent of those patients were able to have CAR T cells manufactured from there, so a 99% manufacturing success rate. There was a 17-day average turnaround time from the cells being shipped out to the centralized manufacturing facility and coming back to the treatment center. Of those 111 enrolled patients, 91% received infusion of axicabtagene ciloleucel. Of those 10 patients who didn’t get the treatment, the majority had adverse events (AEs) due to progressive disease that precluded them getting infusion of CAR T cells.
What were the results presented here?
The primary analysis was triggered when at least 92 patients had the opportunity for 6 months of follow-up. When the 92nd patient was dosed, there were an additional 9 patients already enrolled and so those patients went on to also receive the therapy. Therefore, 101 patients had received axicabtagene ciloleucel and those 101 patients are the modified intention-to-treat population that was prespecified in the protocol, and those are the results we are presenting. Out of those 101 patients, how did they do?