The chimeric antigen receptor (CAR)-T cell therapy CTX130 (volamcabtagene durzigedleucel) showed encouraging results in patients with heavily pretreated relapsed or refractory T-cell lymphoma, according to a phase 1 trial.
“In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate,” the authors, led by Swaminathan Iyer, MD, of The University of Texas MD Anderson Cancer Center in Houston, reported in an article published in The Lancet Oncology.
In the single-arm, open-label trial, 39 patients with peripheral T-cell lymphoma or cutaneous T-cell lymphoma received CTX130,a CD70-directed allogeneic CAR T-cell therapy, following lymphodepletion with fludarabine and cyclophosphamide. Patients were treated across escalating dose levels, ranging from 3 × 10⁷ to 9 × 10⁸ CAR-positive T cells. The primary endpoint was safety, specifically dose-limiting toxicities (DLTs) within 28 days of infusion, while secondary endpoints included the objective response rate (ORR).
With a median follow-up of 7.4 months, the ORR was 46.2% among all participants, with responses improving to 51.6% in those treated at higher dose levels (3 and 4). This included a complete response rate of 19.4% and a partial response rate of 32.3%.
Cytokine release syndrome (CRS) occurred in 67% of patients, predominantly grade 1–2, though three patients experienced severe CRS (grade 3–4). Other notable adverse events included neutropenia (36%), anemia (28%), and thrombocytopenia (15%), with serious adverse events occurring in 36% of patients.
The results of the phase I trial demonstrate the potential of CTX130 as a viable treatment for relapsed or refractory T-cell lymphoma, particularly in patients with limited options, the authors wrote.
“This study shows that allogeneic, readily available CAR-T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development,” the authors concluded.
Funding was provided by CRISPR Therapeutics.
Reference
Iyer SP, Sica RA, Ho PJ, et al. Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. Lancet Oncol. Published online November 28, 2024. doi:10.1016/S1470-2045(24)00508-4
