ZUMA-1, Kite Pharma‘s Phase 1/2 trial assessing the CAR T-cell therapy axicabtagene ciloleucel in patients with aggressive B-cell non-Hodgkin’s lymphoma has reached its primary endpoint of objective response rate, according to recent data presented at the American Association of Cancer Research 2017 Annual Meeting April 1-5 in Washington, D.C.
Frederick L. Locke, MD, the ZUMA-1 co-lead investigator, conducted two presentations revealing positive data from the trial’s primary analysis, including an ongoing response rate of 44% after a median of 8.7 months following a single infusion of axicabtagene ciloleucel.
Locke is director of research for the Immune Cell Therapy Program at Moffitt Cancer Center in Tampa, Florida.
Based on the findings, ZUMA-1 was awarded the Clinical Trial Result of the Year at the Clinical Research Excellence (CARE) Awards, Kite announced in a press release. The award, presented April 5 at a ceremony in Boston, recognizes Kite’s clinical achievements in the pharmaceutical industry and contribution to the advancement of axicabtagene ciloleucel for a disease with unmet needs.
Axicabtagene ciloleucel is a CAR (chimeric antigen receptor) T-cell therapy that removes the patient’s own T-cells and genetically engineers them to recognize the CD19 protein, found at the surface of most lymphoma cells. Then engineered cells are expanded in the lab and injected back into the patient’s bloodstream, where they eliminate tumor cells.
The therapy is currently being investigated in patients with refractory, aggressive NHL in the Phase 1/2 ZUMA-1 trial (NCT02348216). The study includes two groups, one with diffuse large B-cell lymphoma (DLBCL) patients, and one with transformed follicular lymphoma (TFL) or primary mediastinal B-cell lymphoma (PMBCL) patients.
ZUMA-1 enrolled 111 participants, 101 of whom were successfully treated with axicabtagene ciloleucel. Among the participants, 85% had stage 3/4 disease; 79% were refractory to chemotherapy and had not received prior autologous stem cell transplant (ASCT); 21% had received ASCT but relapsed within 12 months; and 69% had received at least three lines of therapy.
Results have now shown that after a median follow-up of 8.7 months, 82% of patients responded to the treatment, and 44% are still ongoing. Complete responses were seen in 54% of patients, with 39% ongoing. Median duration of response was 8.2 months and has not been reached for patients with complete response.
Importantly, patients who were refractory to two or more lines of therapy had an overall response rate of 83%, while those who relapsed within 12 months of ASCT had 76% ORR.
A pooled analysis of refractory aggressive NHL patients with similar characteristics as those included in ZUMA-1 estimated a median overall survival of 6.6 months with currently available therapies, with only 8% of patients achieving complete responses. In ZUMA-1, the median overall survival has not yet been reached.
The most common grade 3 or higher adverse effects included low levels of specific blood cell subtypes.
The researchers reported a decrease in the percentage of patients experiencing cytokine release syndrome (CRS) — a side effect cause by over-activation of the immune system — and neurologic events, compared to the interim analysis.
“We are excited to present the data from the primary analysis of ZUMA-1 at AACR. Close to half of patients treated remained in response, which represents a remarkable result in this heavily treated population with refractory aggressive NHL who previously faced a dismal outlook,” Jeff Wiezorek, MD, senior vice president of clinical development at Kite, said in a press release.
“We believe the rates of CRS and neurologic events decreased over the course of the study as clinicians gained experience in the management of adverse events,” he added.
Kite has recently completed the submission of a Biologics Licence Application (BLA) to the U.S. Food and Drug Administration, requesting axicabtagene ciloleucel approval for relapsing aggressive non-Hodgkin’s lymphoma patients. It also plans to submit a marketing authorization application this year to the European Medicines Agency (EMA) for the same indication.