Leucid Bio's Novel CAR-T Therapy LEU011 Shows Proof-of-Concept in Solid Tumors with Encouraging Safety Profile
核心洞察
Leucid Bio (搜索)'s LEU011, a lateral CAR-T therapy targeting NKG2D stress ligands, has established proof-of-concept in the Phase I/IIa AERIAL trial for treating relapsed/refractory solid tumors (搜索).
The therapy demonstrated tumor infiltration by LEU011 cells in post-treatment biopsies and achieved disease control in multiple patients at the lowest dose tested.
LEU011 features a dual mechanism of action, targeting NKG2D stress ligands for tumor recognition while using CXCR2 (搜索) signaling to enhance T-cell infiltration into the tumor microenvironment.
Leucid Bio (搜索) has announced encouraging preliminary results from its Phase I/IIa AERIAL trial evaluating LEU011, a novel lateral CAR-T cell therapy for patients with relapsed/refractory solid tumors (搜索). The data, presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2025, establish proof-of-concept for the innovative therapy and demonstrate a favorable safety profile.
Proof-of-Concept Established Through Tumor Infiltration
The preliminary data from the ongoing AERIAL trial have demonstrated key biological activity through encouraging pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Notably, analysis of post-treatment biopsies using ddPCR and RNAScope techniques has shown tumor infiltration by LEU011 cells, providing critical evidence of the therapy's mechanism of action.
"Although preliminary, we are highly encouraged by these initial data from the AERIAL trial which establish proof-of-concept for LEU011 in the treatment of solid tumours," said Filippo Petti, Chief Executive Officer of Leucid Bio (搜索). "Furthermore, they highlight LEU011's dual mechanism of action targeting NKG2D stress ligands for tumour recognition and using CXCR2 (搜索) signalling to enhance T-cell infiltration into the tumour microenvironment."
Disease Control Achieved at Lowest Dose
Treatment with LEU011 has been generally well tolerated to date. Significantly, disease control based on RECIST criteria has been observed in multiple patients treated with the lowest dose of LEU011 evaluated in the trial. This early efficacy signal at the lowest dose level suggests potential for improved responses as dose escalation continues.
Novel Dual Mechanism Addresses CAR-T Limitations
LEU011 represents a unique approach to overcoming the traditional challenges of CAR-T therapies in solid tumors (搜索). The therapy targets NKG2D stress ligands, which are overexpressed on more than 80% of human tumor cells and cells within the surrounding tumor microenvironment. Additionally, LEU011 co-expresses the chemokine receptor CXCR2 (搜索), which is engineered to enhance cell trafficking and tumor infiltration.
Dr. John Maher, Chief Scientific Officer at Leucid Bio (搜索), emphasized the significance of these findings: "Traditionally, CAR-Ts have struggled to deliver robust clinical responses in the treatment of solid tumours. We believe these preliminary data highlight the functional activity of LEU011 in the treatment of solid tumours given its unique mechanism of action."
Trial Design and Future Timeline
The AERIAL trial is a multi-center, dose-escalation study designed to evaluate the safety and clinical activity of LEU011 in patients with relapsed/refractory solid tumors (搜索). Patients receive a single intravenous dose of LEU011 following preconditioning chemotherapy. The trial is registered on ClinicalTrials.gov under the identifier NCT06193902.
Dose-escalation in the AERIAL trial continues as planned, with the company anticipating additional data during the first half of 2026. Dr. Maher noted that the team expects "the early signals observed to date for LEU011 will continue to improve as we advance through the dose-escalation segment of the AERIAL trial."
The trial results were presented as a poster titled "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 (搜索) (AERIAL)" by R. Kristeleit during the Clinical Trials In Progress session at SITC 2025.