{
  "abstract": "Background: Cancer of unknown primary (CUP) remains a challenging malignancy with a poor prognosis. Although immune checkpoint inhibitors have shown activity in CUP, available data remains limited. We describe clinical outcomes and a comprehensive biomarker analysis from an expanded access trial of nivolumab in CUP.\n\nMethods: Patients with CUP were enrolled regardless of treatment history and received intravenous nivolumab (240 mg every 2 weeks or 480 mg every 4 weeks) until disease progression, unacceptable toxicity, or withdrawal. Enrollment concluded after regulatory approval of nivolumab for CUP in Japan. The primary objective was safety; secondary endpoints addressed efficacy, and exploratory biomarker analyses were performed.\n\nResults: A total of 53 patients (31 previously treated, 22 untreated) received nivolumab. Adverse events (AEs) occurred in 77.4% of patients, including 24.5% grade 3–4 and 15.1% serious AEs; no treatment-related deaths occurred. The objective response rate was 17.0% (95% confidence interval [CI] 8.1–29.8%) overall and 20.5% (95% CI 9.8–35.3%) in the response-evaluable subset. Median progression-free survival was 4.5 months (95% CI 2.9–7.9) and median overall survival was 17.5 months (95% CI 11.9–25.1). Higher PD-L1 expression was associated with better efficacy, whereas no meaningful differences were observed across estimated tissue-of-origin subgroups.\n\nConclusions: This study provides additional prospective evidence consistent with the preceding NivoCUP trial, supporting the reproducibility of the efficacy and safety of nivolumab for patients with CUP. These findings support PD-1-targeted therapy as a feasible treatment option for this rare malignancy.\n\nTrial registration: Japan Registry of Clinical Trials (jRCT) identifier, jRCT2051200146.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10147-026-03187-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, Kindai University Faculty of Medicine, 1-14-1 Mihara-dai, Minami-ku, Sakai, Osaka 590-0197 Japan",
    "Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan",
    "Medical Oncology Department, Chiba University, Chiba, Japan",
    "Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan",
    "Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan",
    "Division of Clinical Oncology, Shizuoka Cancer Center, Shizuoka, Japan",
    "Department of Medical Oncology, NHO Nagoya Medical Center, Nagoya, Japan",
    "Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan",
    "Department of Medical Oncology, Hyogo Cancer Center, Akashi, Japan",
    "Department of Medicine, Division of Medical Oncology, Graduate School of Medicine, Showa Medical University, Tokyo, Japan",
    "Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan",
    "Department of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Kobe, Japan",
    "Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan",
    "Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan",
    "Department of Pathology, Kindai University Faculty of Medicine, Osaka, Japan",
    "Clinical Research Center, Kindai University Hospital, Osaka, Japan",
    "Department of Tumor Microenvironment, Faculty of Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan",
    "Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan",
    "Kindai University Hospital Cancer Center, Osaka, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
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        0
      ],
      "name": "Junko Tanizaki"
    },
    {
      "affs": [
        1
      ],
      "name": "Kan Yonemori"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuichi Takiguchi"
    },
    {
      "affs": [
        3
      ],
      "name": "Kohei Akiyoshi"
    },
    {
      "affs": [
        4
      ],
      "name": "Keigo Komine"
    },
    {
      "affs": [
        5
      ],
      "name": "Yusuke Onozawa"
    },
    {
      "affs": [
        6
      ],
      "name": "Mariko Sato"
    },
    {
      "affs": [
        7
      ],
      "name": "Kenro Hirata"
    },
    {
      "affs": [
        8
      ],
      "name": "Takuma Onoe"
    },
    {
      "affs": [
        9
      ],
      "name": "Ryotaro Ohkuma"
    },
    {
      "affs": [
        10
      ],
      "name": "Yosuke Horita"
    },
    {
      "affs": [
        11
      ],
      "name": "Hironobu Minami"
    },
    {
      "affs": [
        12
      ],
      "name": "Kazunori Honda"
    },
    {
      "affs": [
        13
      ],
      "name": "Koichi Suyama"
    },
    {
      "affs": [
        14
      ],
      "name": "Akihiko Ito"
    },
    {
      "affs": [
        15
      ],
      "name": "Yasutaka Chiba"
    },
    {
      "affs": [
        16
      ],
      "name": "Hiroko Watanabe"
    },
    {
      "affs": [
        16
      ],
      "name": "Yosuke Togashi"
    },
    {
      "affs": [
        17
      ],
      "name": "Kazuko Sakai"
    },
    {
      "affs": [
        17
      ],
      "name": "Kazuto Nishio"
    },
    {
      "affs": [
        18
      ],
      "name": "Kazuhiko Nakagawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Hidetoshi Hayashi",
      "orcid": "0000-0001-8787-5587"
    }
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  "bibtex": "https://research.draconitic.com/paper/50ps6gz4c9h1k.bib",
  "cited_by": 0,
  "doi": "10.1007/s10147-026-03187-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710682/",
  "id": "50ps6gz4c9h1k",
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    "1437-7772"
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  "landing_url": "https://doi.org/10.1007/s10147-026-03187-9",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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    [
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      "2730|Cancer Diagnosis and Treatment"
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  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s10147-026-03187-9.pdf",
  "pmcid": "PMC13710682",
  "pmid": "42782574",
  "published": "2026-09-24",
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  "ris": "https://research.draconitic.com/paper/50ps6gz4c9h1k.ris",
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  "subjects": [
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      "subfield": "oncology"
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  "title": "Efficacy and biomarker analysis for nivolumab in cancer of unknown primary: results from an investigator-initiated expanded access program",
  "title_text": "Efficacy and biomarker analysis for nivolumab in cancer of unknown primary: results from an investigator-initiated expanded access program",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:36Z",
  "url": "https://research.draconitic.com/paper/50ps6gz4c9h1k",
  "venue": "International Journal of Clinical Oncology",
  "versions": []
}