{
  "abstract": "Background Despite progress in the treatment of advanced non-small cell lung cancer (NSCLC), therapeutic options remain scarce for patients who have developed resistance to immune checkpoint inhibitors (ICIs). THIO (6-thio-2’-deoxyguanosine), a telomere-targeting agent, is selectively recognized by telomerase and integrated into the telomeres of cancer cells. Once incorporated, ateganosine (THIO) compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell apoptosis.Methods THIO-104 is a multicenter, open-label, randomized Phase 3 study enrolling approximately 300 subjects with histologically confirmed advanced/metastatic NSCLC. Eligible participants must have received two prior lines of systemic treatment, including at least one line of ICIs and platinum-based chemotherapy. Participants will be randomized 1:1 to receive either THIO 180 mg per cycle (60 mg IV on Days 1-3 of a 3-week cycle) followed by cemiplimab 350 mg IV on Day 5, or single-agent chemotherapy (vinorelbine, gemcitabine, or docetaxel). The primary endpoint is overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS) and duration of response (DoR).Current Status: Enrollment is ongoing, preliminary safety data and efficacy outcomes will be assessed through scheduled interim analyses.Results and Conclusions THIO-104 will provide critical insights into the potential role of telomere-targeting agents in restoring tumor sensitivity to ICIs in NSCLC. The study will also explore key biomarkers to further characterize THIO’s mechanism of action and it’s potential to predict patient response to therapy.Trial Registration Country approvals: 01-Mar-2022 (Australia) CT-2021-CTN-04933-1 20-Jul-2022 (Hungary) EudraCT Number 2021-005136-34 22-Nov-2022 (Poland) EudraCT Number 2021-005136-34 06-Oct-2022 (Bulgaria) EudraCT Number 2021-005136-34 27-Jul-2023 (United States) IND-163503 02-Dec-2024 (Taiwan) 1139073522 17-Sep-2024 (Turkey) E-661756679-514.02.02-1577145Ethics Approval Country approvals: 01-Mar-2022 (Australia) CT-2021-CTN-04933-1 20-Jul-2022 (Hungary) EudraCT Number 2021-005136-34 22-Nov-2022 (Poland) EudraCT Number 2021-005136-34 06-Oct-2022 (Bulgaria) EudraCT Number 2021-005136-34 27-Jul-2023 (United States) IND-163503 02-Dec-2024 (Taiwan) 1139073522 17-Sep-2024 (Turkey) E-661756679-514.02.02-1577145",
  "authors": [
    {
      "affiliations": [
        "Semmelweis Egyetem Pulmonologiai Klinika, Budapest, Hungary"
      ],
      "name": "Veronika Muller"
    },
    {
      "affiliations": [
        "NewroMed, Lublin, Poland"
      ],
      "name": "Tomasz Jankowski"
    },
    {
      "affiliations": [
        "University Hospital No 4, Lublin, Poland"
      ],
      "name": "Mariola Kowal-Rosinska"
    },
    {
      "affiliations": [
        "Matrai Gyogyintezet, Matrahaza, Hungary"
      ],
      "name": "Laszlo Urban"
    },
    {
      "affiliations": [
        "University of Budapest, Budapest, Hungary"
      ],
      "name": "Tibor Csoszi"
    },
    {
      "affiliations": [
        "Orszagos Onkologiai Intezet, Budapest, Hungary"
      ],
      "name": "Tunde Nagy"
    },
    {
      "affiliations": [
        "Poznan University of Medical Sciences, Poznan, Poland"
      ],
      "name": "Rodryg Ramlau"
    },
    {
      "affiliations": [
        "Synexus Medical Center, Sofia, Bulgaria"
      ],
      "name": "Maria Cholakova"
    },
    {
      "affiliations": [
        "MHAT Heart and Brain EAD Medical Oncology Clinic, Pleven, Bulgaria"
      ],
      "name": "Nataliya Chilingirova"
    },
    {
      "affiliations": [
        "Orszagos Koranyi Pulmonologiai Intezet, Budapest, Hungary"
      ],
      "name": "Szabolcs Soter"
    },
    {
      "affiliations": [
        "MHAT ‘Serdika’, Sofia/Department of Medical Oncology., Sofia, Bulgaria"
      ],
      "name": "Krassimir Koynov"
    },
    {
      "affiliations": [
        "Centrum Medyczne Pratia, Poznan, Poland"
      ],
      "name": "Marek Kotlarski"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Ilgen Mender"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Romina Girotti"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Marcel Mitsunaga"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Oleg Tudos"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Matthew Failor"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Vlad Vitoc"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Sergei Gryaznov"
    },
    {
      "affiliations": [
        "MAIA Biotechnology Inc., Chicago, IL, USA"
      ],
      "name": "Victor Zaporojan"
    }
  ],
  "title": "563 A phase 3 study of ateganosine (THIO) sequenced with immune checkpoint inhibitor (ICI) versus standard of care chemotherapy in ICI-resistant advanced NSCLC: THIO-104 trial in progress",
  "uid": "066e39bc-e909-5c44-bcc5-08c22a8ca689"
}