{
  "abstract": "Purpose:: XRD-0394 is a dual ataxia-telangiectasia mutated and DNA-dependent protein kinase inhibitor designed to increase tumor radiosensitivity. We evaluated the safety, pharmacokinetics, and pharmacodynamics of single-dose XRD-0394 administered with palliative radiation therapy (RT) in a first-in-human trial.\n\nMethods and Materials:: In an open-label, multicenter phase 1a dose-escalation study, XRD-0394 (40, 80, or 160 mg) was given once, 90 ± 30 minutes before fraction 2 of palliative RT. Primary endpoints were dose-limiting toxicities and tolerability; a coprimary objective was achieving a prespecified plasma exposure target (≥530 ng/mL [1 μM] at 1–4 hours postdose). Exploratory pharmacodynamic activity was assessed by phosphorylated KRAB-associated protein 1 immunohistochemistry in tumor biopsies.\n\nResults:: Twelve participants were treated. No dose-limiting toxicities occurred and the maximum tolerated dose was not reached. Treatment-related adverse events were limited to grade 1 nausea and diarrhea (n = 2), with no treatment-related serious adverse events. At 160 mg, exposures met the prespecified target and supported selection for further development.\n\nConclusions:: Single-dose XRD-0394 can be safely combined with palliative RT at plasma exposures that exceeded the prespecified target threshold, supporting fractionated multidose studies.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Oncology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California",
    "Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California",
    "XRad Therapeutics, Orlando, Florida",
    "PRolific Research Consulting, Punta Gorda, Florida",
    "ClinPharm Advantage, Durham, North Carolina",
    "PharStat Inc, Raleigh, North Carolina",
    "Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina",
    "Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York",
    "Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada",
    "Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada",
    "Department of Thoracic Radiation Oncology, Division of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas",
    "Department of Radiation Oncology, Colorectal and Anal Cancer Service, Memorial Sloan Kettering Cancer Center, New York, New York",
    "Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, New York"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Christopher T. Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Michael F. Gensheimer"
    },
    {
      "affs": [
        2
      ],
      "name": "Tona M. Gilmer"
    },
    {
      "affs": [
        3
      ],
      "name": "Jennifer Stanley"
    },
    {
      "affs": [
        4
      ],
      "name": "Deborah Smith"
    },
    {
      "affs": [
        5
      ],
      "name": "Lei Fang"
    },
    {
      "affs": [
        6
      ],
      "name": "Michael B. Kastan"
    },
    {
      "affs": [
        1
      ],
      "name": "Quynh-Thu Le"
    },
    {
      "affs": [
        7
      ],
      "name": "Simon N. Powell"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "David G. Kirsch"
    },
    {
      "affs": [
        10
      ],
      "name": "Steven H. Lin"
    },
    {
      "affs": [
        7
      ],
      "name": "Jonathan T. Yang"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Paul B. Romesser"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ca29pnjkvg6wa.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ijrobp.2026.08.069",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734973/",
  "id": "ca29pnjkvg6wa",
  "issns": [
    "0360-3016",
    "1879-355X"
  ],
  "landing_url": "https://doi.org/10.1016/j.ijrobp.2026.08.069",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2741|Effects of Radiation Exposure"
    ]
  ],
  "openalex": "W7212264188",
  "pdf_url": "https://www.redjournal.org/article/S0360-3016(26)04283-5/pdf",
  "pmcid": "PMC13734973",
  "pmid": "42727889",
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ca29pnjkvg6wa.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:45Z",
      "native_id": "PMC13734973",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ijrobp.2026.08.069"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Effects of Radiation Exposure",
      "subfield": "imaging"
    }
  ],
  "title": "Phase 1a Clinical Trial of XRD-0394, a First-in-Class Dual Ataxia-Telangiectasia Mutated and DNA-Dependent Protein Kinase Inhibitor, in Combination With Palliative Radiation Therapy",
  "title_text": "Phase 1a Clinical Trial of XRD-0394, a First-in-Class Dual Ataxia-Telangiectasia Mutated and DNA-Dependent Protein Kinase Inhibitor, in Combination With Palliative Radiation Therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:45Z",
  "url": "https://research.draconitic.com/paper/ca29pnjkvg6wa",
  "venue": "International journal of radiation oncology, biology, physics",
  "versions": []
}