{
  "abstract": "Background There is a significant unmet need for effective therapies for patients with solid tumours refractory to standard of care. The majority of solid tumours express NKG2D ligands (NKG2DL), whilst the tumor microenvironment commonly produces CXCR2-specific chemokines to promote tumour progression via the recruitment of immunosuppressive myeloid cells. LEU011 is an autologous adaptor CAR T-cell product targeted against NKG2DL. Trafficking to solid tumors is enhanced by co-expression of the CXCR2 chemokine receptor. Preclinical studies showed that LEU011 mediated enhanced functional persistence, trafficking to and regression of multiple solid tumor models, when compared to an analogue of a clinical stage NKG2D-based linear CAR. The trial hypothesis is that LEU011, combined with lymphodepleting chemotherapy (LDC), will be safe and tolerable, and will elicit efficacy in patients with NKG2DL-expressing tumors.Methods NCT06193902Study Design: Phase I/IIa, open-label, multicenter study• Intervention: LDC followed by single infusion of LEU011 (figure 1)Patient Population: adult subjects with histologically confirmed relapsed/refractory solid tumors for which no standard treatment options are available, specifically requiring expression of one or more NKG2D ligands on 10% or more cells and the presence of measurable disease. Key eligibility includes good performance status (ECOG 0-1), adequate organ function, a washout period ≥28 days from prior anti-cancer therapies (except LDC), no active infections or major co-morbidities.Endpoints: The primary endpoints for this trial are the incidence and nature of dose-limiting toxicities and the incidence, nature, and severity of adverse events.Trial Registration This trial ‘LEU01101: Safety and Preliminary Efficacy of LEU011 in Solid Tumours’ is registered at ClinicalTrials.gov with the unique reference number NCT06193902Ethics Approval Ethical approval for this clinical trial was granted by the North East - York Research Ethics Committee under REC reference 23/NE/0097. All participants provided informed consent prior to enrollment onto the trial.Abstract 578 Figure 1Trial schematic",
  "authors": [
    {
      "affiliations": [
        "GSTT, London, UK"
      ],
      "name": "Rebecca Kristeleit"
    },
    {
      "affiliations": [
        "King’s College London, London, UK",
        "Leucid Bio, London, UK",
        "Eastbourne Hospital, Eastbourne, East Sussex, UK"
      ],
      "name": "John Maher"
    },
    {
      "affiliations": [
        "Leucid Bio, London, UK"
      ],
      "name": "Marc Davies"
    },
    {
      "affiliations": [
        "Leucid Bio, London, UK"
      ],
      "name": "Arindam Mitra"
    },
    {
      "affiliations": [
        "Leucid Bio, London, UK"
      ],
      "name": "Roisin Beehag"
    },
    {
      "affiliations": [
        "Leucid Bio, London, UK"
      ],
      "name": "Belinda Carlsen"
    },
    {
      "affiliations": [
        "Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Chen Han Yong"
    },
    {
      "affiliations": [
        "Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Linda Gomm"
    },
    {
      "affiliations": [
        "Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Debra Josephs"
    },
    {
      "affiliations": [
        "Leucid Bio, London, UK",
        "Omniac Pharm consult Ltd, London, UK"
      ],
      "name": "Zahid Bashir"
    },
    {
      "affiliations": [
        "The Christie NHS Foundation Trust and University of Manchester, Manchester, UK",
        "The University of Manchester, Manchester, UK"
      ],
      "name": "Fiona Thistlethwaite"
    }
  ],
  "title": "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)",
  "uid": "8bf75daf-6f60-51c3-89e9-e807f98e3683"
}