Results from the phase I ZUMA-1 trial presented at the AACR Annual Meeting suggest that KTE-C19, a chimeric antigen receptor (CAR), is a safe treatment option for patients with non-Hodgkin lymphoma (NHL).
"Anti-CD19 CAR T cells with CD3 zeta and CD28 signaling domains showed durable remissions in subjects with relapsed/refractory advanced B-cell malignancies [in an earlier National Cancer Institute trial]," the study authors, led by Armin Ghobadi, MD, from the Siteman Cancer Center at the Washington University School of Medicine in St. Louis, Missouri, explained. "KTE-C19 uses the same CAR construct as investigated in the NCI study in a six- to eight-day manufacturing process."
The updated results of the ZUMA-1 trials presented by Dr. Ghobadi and colleagues include data from seven adult patients (enrolled as of November 20, 2015) with diffuse large B-cell lymphoma who received KTE-C19 at a dose of 2×106 anti-CD19 CAR T cells/kg, after a fixed-dose conditioning chemotherapy regimen consisting of cyclophosphamide and fludarabine.
The study's primary endpoint was safety (determined by the incidence of dose-limiting toxicities), and secondary endpoints included overall response rate, duration of response, and biomarkers.
Patients were eligible for inclusion if they had:
- An Eastern Cooperative Oncology Group score 0-1
- Chemotherapy-refractory disease (defined as progressive disease or stable disease [SD] as the best response to last line of therapy)
- Disease progression within 12 months post-autologous hematopoietic cell transplantation
After a median follow-up of 13 weeks post-KTE-C19 infusion, all patients were evaluable for safety and six were evaluable for efficacy.
The most commonly reported toxicities included cytokine release syndrome (CRS) and neurotoxicity, which were generally reversible and managed with supportive care, Î±-IL6R, and steroids. One patient experienced a dose-limiting toxicity of grade 4 encephalopathy and grade 4 CRS; this patient later died due to an intracranial hemorrhage deemed unrelated to KTE-C19 treatment (per the investigator).
"The KTE-C19 regimen was safe for further study," Dr. Ghobadi and colleagues concluded.
Five of the seven patients (71%) responded to treatment: four complete responses, one partial response, one case of stable disease, and one response that was not evaluable. CAR T cells peaked within two weeks of treatment and were detectable one to three months post-infusion.
These preliminary results in this small population are being further confirmed in a "potentially pivotal" phase II portion of ZUMA-1, which is ongoing, the authors noted.
Ghobadi A, Locke FL, Neelapu SS, et al. Updated phase I results from ZUA-1: A phase I-II multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with refractory aggressive non-Hodgkin lymphoma (NHL). Abstract CT135. Presented at the AACR Annual Meeting, April 19, 2016; New Orleans, LA.