Abstract LB468: Pharmacokinetics of ALETA-001, a CRUK first-in-human phase I/II trial in patients who have received anti-CD19 CAR T-cell therapy for B-cell malignancies

Abstract Background: Antigen loss or escape represents a primary mechanism of treatment failure of anti-CD19 CAR T-cell therapy and results in subsequent disease relapse. ALETA-001 is a first-in-class CAR T-cell engager protein that can bridge anti-CD19 CAR T-cells to cancer cells expressing CD20. Following successful preclinical studies, a first-in-human phase I/II trial of ALETA-001 was initiated in patients with B-cell malignancies. We report the pharmacokinetics of ALETA-001 in this ongoing Cancer Research UK phase I/II study. Methods: Eligible patients were diagnosed with B-cell malignancies and had undergone anti-CD19 CAR T-cell therapy. ALETA-001 was administered intravenously as a 2 hour infusion every 2 weeks, with patients receiving 0.4-2.0 mg/kg in cycle 1, and 2.0-6.0 mg/kg in subsequent cycles. Samples for pharmacokinetic analysis were obtained from cycles 1 and 2 at 0, 0.25, 2, 5, 24, 72 and 168 hours post-ALETA-001 administration, and analyzed using a validated ELISA assay. Pharmacokinetic analysis was carried out to determine parameters including Cmax, area under the curve (AUC), terminal elimination half-life (T1/2), total body clearance (CL), and volume of distribution (Vz) of ALETA-001. Results: Table 1 provides a summary of the pharmacokinetic parameters obtained following ALETA-001 administration (data expressed as range or mean ± SD as appropriate). Comparison of pharmacokinetic data generated following ALETA-001 doses of 0.4 - 6.0 mg/kg suggests general dose proportionality in terms of observed Cmax and AUC values. Estimates of drug half-life in the current patient cohort indicate an elimination half-life of approximately 4-7 days. Conclusion: Novel pharmacokinetic data for the first-in-class CAR T-cell engager protein ALETA-001 have been generated as part of a first-in-human phase I/II clinical trial. Citation Format: Martin Galler, David Jamieson, Paul Rennert, Jenny Craigen, Gareth Veal. Pharmacokinetics of ALETA-001, a CRUK first-in-human phase I/II trial in patients who have received anti-CD19 CAR T-cell therapy for B-cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB468.