In a phase I dose-escalation study (COBALT-LYM) reported in The Lancet Oncology, Iyer et al found that CTX130 (volamcabtagene durzigedleucel)—a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells—had a manageable safety profile and showed activity in patients with relapsed or refractory T-cell lymphoma.
Study Details
In the study, 39 eligible patients were enrolled at sites in the United States, Australia, and Canada between August 2020 and May 2023. Patients received lymphodepletion with fludarabine at 30 mg/m² and cyclophosphamide at 500 mg/m² daily for 3 days, followed by CTX130 infusion at four CAR T dose levels: level 1 = 3 × 107 (n = 4); level 2 = 1 × 10⁸ (n =4); level 3 = 3 × 10⁸ (n = 5); or level 4 = 9 × 10⁸ (n = 26). The median number of previous lines of anticancer therapy was 2.5 (interquartile range [IQR] = 1.3–4.0) among patients with peripheral T-cell lymphoma and 5.0 (IQR = 5.0–7.0) among those with cutaneous T-cell lymphoma.
Key Findings
Cytokine-release syndrome was the most common adverse event, occurring in 26 of 39 patients (67%); 23 cases were grade 1 or 2, 2 were grade 3, and 1 was a grade 4 dose-limiting toxicity at dose level 4. Grade 1 or 2 neurotoxic events were observed in four patients (10%). The most common grade 3 or 4 adverse events were neutropenia (36%), anemia (28%), and thrombocytopenia (15%). CTX130-related serious adverse events were reported in 36% of patients, most commonly cytokine-release syndrome (28%). Adverse events led to death in five patients, with none considered related to CTX130.
Objective responses were observed in 18 patients (46.2%, 95% confidence interval [CI] = 30.1%–62.8%). Among the 31 patients receiving dose level 3 or 4, objective responses were observed in 16 patients (51.6%, 95% CI = 33.1%–69.8%), including complete response in 6 (19.4%, 95% CI = 7.5%–37.5%).
The investigators concluded: “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 relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development.”
Swaminathan P. Iyer, MD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by CRISPR Therapeutics. For full disclosures of the study authors, visit thelancet.com.
