NATICK, Mass.– Aleta Biotherapeutics and Cancer Research UK’s Centre for Drug Development have released preliminary findings from an ongoing phase I/II study evaluating ALETA-001 in patients with relapsed or refractory B-cell malignancies previously treated with CD19-targeted CAR T-cell therapy. Early data indicate that the investigational biologic has been well tolerated across all tested dose levels and has shown initial signs of clinical activity in patients who did not achieve, or who lost, remission after CAR T-cell therapy.
The multi-center, open-label study (NCT06045910) is being conducted at sites across the United Kingdom. The trial is assessing safety, tolerability, dosing and early efficacy signals of ALETA-001, a CAR T-cell engager intended to enhance the activity of CD19-directed CAR T-cell therapies. Doses range from 0.4 mg/kg to 6.0 mg/kg, with two phase I cohorts testing different dosing schedules before the phase II expansion.
One cohort includes patients who were at least four weeks removed from CD19 CAR T-cell infusion and had either not reached a complete metabolic remission (CMR) on PET/CT or had achieved an initial CMR but relapsed within nine months. Investigators reported that ALETA-001 produced no related serious adverse events above Grade 1 at any dose level. In four of six patients treated at the lowest doses, CAR T-cell expansion was observed, consistent with the expected mechanism of action. Some patients in this cohort also showed encouraging responses, including durable CMRs after receiving ALETA-001.
A second cohort is evaluating ALETA-001 earlier in the treatment window, between 10 and 18 days after CAR T-cell infusion. These patients have shown no toxicity to date and are being monitored for biomarker changes and durable responses.
Sridhar Chaganti, MD, PhD, Chief Investigator at University Hospitals Birmingham NHS Foundation Trust, said the early findings address a critical clinical need. “The majority of B-cell lymphoma patients relapse early after CD19-targeted CAR T-cell therapy. For these patients, time is critical and outcomes with further treatments are poor. ALETA-001 is a promising, off-the-shelf therapeutic that increases and maintains CD19 antigen density, thereby optimizing CD19-targeted CAR T-cell activity and offering the potential for a cure.”
Marco Ruella, MD, Associate Professor of Medicine at the University of Pennsylvania and advisor to Aleta Biotherapeutics, noted the implications for CAR T-cell performance. “Having agents that can enhance or even rescue CAR T-cell anti-tumor activity is highly desirable,” he said. “These promising preliminary clinical results initially suggest that ALETA-001 can revitalize CAR T-cells that have struggled to clear the tumor.”
Paul Rennert, President and Chief Scientific Officer at Aleta Biotherapeutics, said the data support the investigational agent’s proposed mechanism. “The data presented by Dr. Chaganti and colleagues provide proof of mechanism for ALETA-001,” he said. “This is an exciting milestone. ALETA-001 is now being provided to patients shortly after they receive a CD19 CAR T-cell therapy, giving these patients the opportunity for a robust and durable response.”
The trial is sponsored and conducted by Cancer Research UK’s Centre for Drug Development. The organizations plan to add more clinical sites across the United Kingdom in 2026 to broaden patient access.
