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Lymphoma: Dual-Targeting CAR T Shows Safety, Efficacy
In a first in-human study, KITE-363, an anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy, showed high rates of response in patients with highly refractory large B-cell lymphoma (LBCL). The bicistronic, autologous CAR T-cell therapy, designed to prevent CD19 escape through the upfront targeting of CD19 and CD20, also showed an encouraging safety profile, with no dose-limiting toxicities.
METHODOLOGY:
The phase 1, open-label, multicenter study enrolled adult patients with LBCL, indolent non-Hodgkin lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, or mediastinal gray zone lymphoma.
Following lymphodepleting chemotherapy, patients were treated with KITE-363 at dose levels of 1, 2, or 3, corresponding to 0.5 × 10 6 , 1 × 10 6 , and 2 × 10 6 CAR T cells per kilogram, respectively.
, 1 × 10 , and 2 × 10 CAR T cells per kilogram, respectively. Among 37 patients who were eligible and treated, the majority (73%) had advanced stage III or IV disease, and all were highly refractory, with more than two prior lines of therapy.
The median age of patients was 62 years, with more than 10% of those in the study older than 75 years.
TAKEAWAY:
At a median follow-up of 11.2 months, the outcomes for CAR T-naive patients treated at dose level 3 (n = 23; 2 × 10 6 CAR T cells per kilogram), which is the recommended dose for phase 2 trials, showed an overall response rate (ORR) of 87%, while the complete response (CR) rate was 78%.
CAR T cells per kilogram), which is the recommended dose for phase 2 trials, showed an overall response rate (ORR) of 87%, while the complete response (CR) rate was 78%. All seven patients (100%) with LBCL who were CAR T-naive after two or more lines of therapy and who received dose level 3 had a CR. Of the 15 patients receiving dose level 3 who were primary refractory, the ORR was 80% and the CR rate was 67%.
The median duration of CR was not reached, while the 6-month duration of CR was 71.4%.
Overall, no dose-limiting toxicities occurred.
There were no grade 3 or higher reports of cytokine release syndrome (CRS). Two cases of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred with short durations; however, no cases occurred among those receiving dose level 3, with primary refractory LBCL (n = 15).
IN PRACTICE:
'KITE-363 demonstrated high responses in patients with highly refractory LBCL, including those with primary refractory disease,' said first author Saurabh Dahiya, MD, of the Stanford University School of Medicine, in Stanford, California. 'We observed no grade 3 or 4 CRS or ICANS in this study, which is a sharp contrast to the current FDA-approved CAR T-cell therapies,' he said.
'Taken together, these results support KITE-363 as a promising therapeutic approach for patients with R/R [relapsed or refractory] B-cell lymphoma, including those with highly refractory LBCL,' Dahiya added. 'Given the promising early results and specifically robust CAR T expansion and good safety profile, KITE-363 is now being developed for the treatment of autoimmune conditions.'
SOURCE:
This study was presented in Chicago at American Society of Clinical Oncology (ASCO) 2025.
DISCLOSURES:
This study was funded by Kite, a Gilead Company.
