{
  "abstract": "Background Pancreatic ductal adenocarcinoma (PDAC) remains an indication of immense clinical need. KRAS mutation is a hallmark of most PDAC cases, and several groups are now studying the use of mutant KRAS-selective TCR-modified T-cell therapy (TCR-T). A significant proportion of PDAC patients benefit from initial standard-of-care (SOC) chemotherapy, but progress later due to chemotherapy resistance. We hypothesize that PDAC patients with at least stable disease after SOC first-line chemotherapy will have a therapeutic benefit from additional TCR-T.A highly potent TCR specific for KRAS G12V restricted by A*11:01 has been developed1 and is available for autologous TCR-T via an approved GMP process incorporating gene-editing and recovery of purified CD8+ TCR+ TCR-T cells. This TCR-T product is designated ANOC-001Methods Registration : EUCT 2024-513900-32-00Study Design: Phase I/IIa, open-label, multicentre studyIntervention: SOC followed by low-dose lymphodepletion and single infusion of ANOC-001Patient Population: Adult subjects with locally advanced or metastatic PDAC, with disease control after c.16 weeks of SOCThe ANOC-001 sub-study of VIDAR-1 is opening at eight centres in the EU. Adult HLA- and mutation-matched PDAC patients with newly diagnosed metastatic or locally advanced non-resectable disease are eligible. The phase 1 part follows a 3+3 dose escalation design with two dose levels to determine safety and tolerability of ANOC-001 and establish the recommended phase 2 dose (RP2D). In a phase 2a extension part up to 20 patients will be treated at the RP2D to preliminarily assess the anti-tumour activity of ANOC-001. Leukapheresis to collect autologous T-cell inputs for ANOC-001 manufacturing takes place before or within early cycles of SOCTrial Registration EUCT 2024-513900-32-00Reference Salter, et al. Preclinical development of TCR-modified T cell therapies against mutated KRAS. Annals Oncol. 2024;35:S694-S694.Ethics Approval At country-level obtained during CTIS part II evaluation of EUCT 2024-513900-32-00.",
  "authors": [
    {
      "affiliations": [
        "Anocca AB, Södertälje, Sweden"
      ],
      "name": "Hugh Salter"
    },
    {
      "affiliations": [
        "Leucid Bio, London, London, UK"
      ],
      "name": "Zahid Bashir"
    },
    {
      "affiliations": [
        "University Hospital and Faculty of Medicine Eberhard Karls University Tubingen, Tubingen, Germany"
      ],
      "name": "Wolfgang Bethge"
    },
    {
      "affiliations": [
        "University Hospital and Faculty of Medicine Eberhard Karls University Tubingen, Tubingen, Germany"
      ],
      "name": "Michel Bitzer"
    },
    {
      "affiliations": [
        "Charité-Universitätsmedizin Berlin, Berlin, Berlin, Germany"
      ],
      "name": "Antonia Busse"
    },
    {
      "affiliations": [
        "Karolinska University Hospital, Huddinge, Sweden"
      ],
      "name": "Mattias Carlsten"
    },
    {
      "affiliations": [
        "Copenhagen University Hospital – Herlev and Gentofte, Herlev, Copenhagen, Denmark"
      ],
      "name": "Inna M Chen"
    },
    {
      "affiliations": [
        "Radhoud University Medical Centre, Nijmegen, Netherlands"
      ],
      "name": "Ingrid ME Desar"
    },
    {
      "affiliations": [
        "Radhoud University Medical Centre, Nijmegen, Netherlands"
      ],
      "name": "Carla van Herpen"
    },
    {
      "affiliations": [
        "Karolinska University Hospital, Solna, Sweden"
      ],
      "name": "Maximilian Kordes"
    },
    {
      "affiliations": [
        "University Hospital Heidelberg, Heidelberg, Germany"
      ],
      "name": "Christoph Springfeld"
    },
    {
      "affiliations": [
        "Uniklinik Dresden, Dresden, Saxony, Germany"
      ],
      "name": "Martin Wermke"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centres, Amsterdam, Netherlands"
      ],
      "name": "Johanna Wilmink"
    },
    {
      "affiliations": [
        "Anocca AB, Södertälje, Sweden"
      ],
      "name": "Reagan Jarvis"
    }
  ],
  "title": "543 VIDAR-1: a phase 1/2a master protocol for open-label, multi-centre, single-arm, first-in-human clinical studies of autologous TCR-T therapy targeting mutant KRAS in metastatic or locally advanced PDAC",
  "uid": "28e91397-b5fc-5653-8313-5200b5980ecf"
}