The ZUMA-23 trial, which will compare axicabtagene ciloleucel with the standard of care in patients with high-risk large B-cell lymphoma (LBCL), is now open for enrollment.
ZUMA-23 will be the first phase III randomized controlled study to evaluate chimeric antigen receptor (CAR) T-cell therapy as a frontline regimen for any cancer, according to a presentation by Jason Westin, MD, of the MD Anderson Cancer Center, at the 2023 American Society of Clinical Oncology Annual Meeting.
The trial will enroll around 300 patients with high-risk, histologically confirmed LBCL as defined by the 2016 World Health Organization classification. The study will include patients with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), and transformed follicular lymphoma or marginal zone lymphoma. Patients who have a history of HIV or hepatitis B or C and undetectable viral loads may enroll. Key exclusion criteria include LBCL of the central nervous system.
Patients who are eligible will receive one cycle of rituximab chemotherapy before the investigators randomize patients 1:1 to receive axicabtagene ciloleucel or standard of care. Patients who are randomized to receive axicabtagene ciloleucel will undergo leukapheresis followed by bridging therapy with R-CHOP or DA-EPOCH-R. Patients will then receive lymphodepleting chemotherapy and a single infusion of axicabtagene ciloleucel at a dose of 2×106 CAR T cells/kg.
“Prophylactic corticosteroids may be administered to reduce the incidence and severity of cytokine release syndrome at the investigator’s discretion,” according to Dr. Westin and colleagues.
Patients who are randomized to receive the standard of care will undergo five additional cycles of R-CHOP or DA-EPOCH-R based on investigator’s choice.
The trial’s primary endpoint is event-free survival by blinded central review. Overall survival and progression-free survival are “key secondary endpoints,” according to the study’s investigators.
The ZUMA-23 trial follows the approval of axicabtagene ciloleucel for relapsed or refractory LBCL. The autologous CD19-directed CAR-T therapy showed “significant clinical benefit” as a second-line therapy in ZUMA-7 and a third-line or later therapy in ZUMA-1, according to Dr. Westin and colleagues. It also showed a “high rate of durable responses” in the phase II ZUMA-12 study of patients with first-line refractory LBCL, they said.
Westin J, Jacobson CA, Chavez JC, et al. ZUMA-23: A global, phase 3, randomized controlled study of axicabtagene ciloleucel versus standard of care as first-line therapy in patients with high-risk large B-cell lymphoma. Abstract TPS7578. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.