During the Society of Immunotherapy of Cancer (SITC) 2025 Annual Meeting, held November 5 – 9 at the Gaylord National Resort and Convention Center in National Harbor, Maryland, researchers from Leucid Bio, a biotechnology company developing innovative Chimeric Antigen Receptor T-cell (CAR-T) therapies using its proprietary lateral CAR platform, presented an update on the phase 1/2a AERIAL trial (NCT06193902) evaluating the safety and clinical activity of LEU011, combined with lymphodepleting chemotherapy (LDC), in patients with relapsed/refractory solid tumors.[1]
LEU011 has been well tolerated, with disease control observed in multiple patients at lowest dose evaluated to date
LEU011 is a lateral CAR T-cell therapy targeting NKG2D stress ligands, which are overexpressed on more than 80% of human tumour cells and the cells within the surrounding tumor microenvironment.
In addition to its novel architecture, LEU011 also co-expresses the chemokine receptor CXCR2, engineered to enhance cell trafficking and tumor infiltration, providing an additional mechanism to overcome the significant limitations of CAR T-cell therapies currently in development for the treatment of relapsed/refractory solid tumours.
Proof of Concept
Preliminary data from the ongoing AERIAL trial have established proof of concept for LEU011 by demonstrating key biological activity through encouraging pharmacokinetic (PK) and pharmacodynamic (PD) profiles. In particular, analysis of post-treatment biopsies (as evaluated by ddPCR and RNAScope) has shown tumour infiltration by LEU011 cells.
To date, treatment with LEU011 has been generally well tolerated. In addition, disease control (based on RECIST criteria) has been observed in multiple patients treated with the lowest dose of LEU011. Dose escalation in the AERIAL trial continues as planned, with additional data anticipated during the first half of 2026.
“Although preliminary, we are highly encouraged by these initial data from the AERIAL trial, which establishes proof-of-concept for LEU011 in the treatment of solid tumors,” note Filippo Petti, Chief Executive Officer, Leucid Bio.
“Also, they highlight LEU011’s dual mechanism of action targeting NKG2D stress ligands for tumour recognition and using CXCR2 signalling to enhance T-cell infiltration into the tumour microenvironment,” Petti added.
“Traditionally, CAR T-cells have struggled to deliver robust clinical responses in the treatment of solid tumours. We believe these preliminary data highlight LEU011’s functional activity in the treatment of solid tumors, given its unique mechanism of action,” John Maher, MD, Chief Scientific Officer, Leucid Bio, who is also a Clinician Scientist at King’s College London, UK, and a Consultant Immunologist at Eastbourne District General Hospital (DGH), is a National Health Service (NHS) hospital in Eastbourne, East Sussex, England.
“We anticipate that the early signals observed to date for LEU011 will continue to improve as we advance through the dose-escalation segment of the AERIAL trial,” Maher concluded.
Clinical trials
LEU01101: Safety and Preliminary Efficacy of LEU011 in Solid Tumors. (AERIAL) – ClinicalTrials.gov ID NCT06193902
Reference
[1] Kristeleit R, Maher J, Davies M, Mitra A, Beehag R, Carlsen B, et al. 578 A First-in-human phase I/IIa dose escalation trial evaluating the safety and preliminary efficacy of LEU011, a novel CAR-T, in subjects with relapsed/refractory solid tumors (AERIAL). Journal for ImmunoTherapy of Cancer. 2025;13:. https://doi.org/10.1136/jitc-2025-SITC2025.0578
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