Multinational phase 1 dose-escalation study of CTX130 for relapsed or refractory T-cell malignancies

Effective treatment options are scarce for relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) or cutaneous T-cell lymphoma (R/R CTCL). CTX130 (volamcabtagene durzigedleucel) is a CD70-directed, allogeneic CAR immunotherapy manufactured from healthy donor T cells. The multinational phase 1 COBALT-LYM trial, at ten centers in Australia, Canada, and the United States, evaluated CTX130 for heavily pretreated R/R PTCL and R/R CTCL. Among 39 patients receiving CTX130 (median follow-up 7.4 months), cytokine release syndrome was observed in 26 patients (67%): 23 were grade 1 or 2, two were grade 3, and one was a grade 4 dose-limiting toxicity. Grade 1 or 2 neurotoxic events were observed in four patients (10%). Twenty-one patients died, 16 from progressive disease and five from adverse events considered unrelated to CTX130 treatment. Objective response was seen in 18 of 39 patients (46.2%; 95% CI 30.1-62.8). The authors conclude that in patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with R/R PTCL or CTCL.