{
  "abstract": "Purpose:: Tinengotinib, a multikinase inhibitor targeting Aurora kinases A/B, fibroblast growth factor receptors (FGFRs) 1 to 3, vascular endothelial growth factor receptor 2, and Janus kinases 1 to 2, was evaluated in this phase Ib/II study to assess safety, pharmacokinetics (PK), efficacy, and genomic correlates of response and resistance in patients with advanced solid tumors.\n\nPatients and Methods:: Patients with advanced/metastatic solid tumors lacking standard treatment options were enrolled at 7 sites in the United States (NCT04742959). Tinengotinib was administered at 12 mg once daily in arm A and at multiple dose levels/dosing schedules in arm C.\n\nResults:: Among 197 patients receiving tinengotinib, treatment-related treatment-emergent adverse events occurred in 160 (81.2%) patients, with hypertension being the most common. Hyperphosphatemia and ocular toxicities were uncommon. Clinical benefit was achieved by 43 of 159 (27.0%) evaluable patients, including 1 complete response, 20 partial responses, and 22 stable diseases ≥6 months. Antitumor activity was most pronounced with 10-mg and 12-mg dose levels. The objective response rates were 33.3%, 30%, and 13% in prostate cancer (n = 15), breast cancer (n = 20), and cholangiocarcinoma (n = 23), respectively. PK analyses supported the 10-mg once-daily regimen. Exploratory genomic analyses identified potential molecular correlations of response, including FGFR2 fusions in cholangiocarcinoma responders. Additional observations in breast cancer, including ROS1 alterations, were exploratory and should be considered hypothesis generating. Exploratory analyses also suggested associations between EGFR or MLL mutations in cholangiocarcinoma and MYC alterations in prostate cancer with shorter progression-free survival, consistent with emerging evidence linking MYC-driven lineage plasticity to androgen receptor–independent disease biology. Reductions in circulating tumor DNA variant allele frequency further supported pharmacodynamic target engagement.\n\nConclusions:: Tinengotinib demonstrated manageable toxicity with antitumor activity across advanced solid tumors, with infrequent hyperphosphatemia and ocular toxicities. Integrated PK–biomarker analyses support the continued clinical development of tinengotinib and the exploration of biomarker-informed precision oncology strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.",
    "Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, Illinois.",
    "Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, California.",
    "Department of Oncology, Gabrail Cancer Center, Canton, Ohio.",
    "Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.",
    "Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.",
    "TransThera Sciences (US), Inc., Gaithersburg, Maryland.",
    "TransThera Sciences (Nanjing), Inc., Nanjing, China.",
    "Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.",
    "Department of Medical Oncology, Rutgers Cancer Center Institute, New Brunswick, New Jersey."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sarina A. Piha-Paul",
      "orcid": "0000-0001-9455-1660"
    },
    {
      "affs": [
        1
      ],
      "name": "Chih-Yi Liao",
      "orcid": "0000-0002-5114-3162"
    },
    {
      "affs": [
        2
      ],
      "name": "Farshid Dayyani",
      "orcid": "0000-0002-4970-5189"
    },
    {
      "affs": [
        3
      ],
      "name": "Nashat Y. Gabrail",
      "orcid": "0009-0007-3885-3622"
    },
    {
      "affs": [
        4
      ],
      "name": "Syed Mohammad Ali Kazmi",
      "orcid": "0000-0002-3367-367X"
    },
    {
      "affs": [
        5
      ],
      "name": "Sayeh Moazami Lavasani",
      "orcid": "0000-0002-3659-1960"
    },
    {
      "affs": [
        6
      ],
      "name": "Katie Hennessy",
      "orcid": "0009-0005-1899-4642"
    },
    {
      "affs": [
        7
      ],
      "name": "Shumao Ni",
      "orcid": "0000-0001-6891-2936"
    },
    {
      "affs": [
        7
      ],
      "name": "Caixia Sun",
      "orcid": "0009-0009-9426-4157"
    },
    {
      "affs": [
        7
      ],
      "name": "Hui Wang",
      "orcid": "0009-0004-5700-5934"
    },
    {
      "affs": [
        7
      ],
      "name": "Peng Peng",
      "orcid": "0000-0003-4230-6086"
    },
    {
      "affs": [
        7
      ],
      "name": "Frank Wu",
      "orcid": "0000-0001-9927-739X"
    },
    {
      "affs": [
        8
      ],
      "name": "Milind M. Javle",
      "orcid": "0000-0001-9158-0941"
    },
    {
      "affs": [
        6
      ],
      "name": "Jean Fan",
      "orcid": "0009-0008-4984-8527"
    },
    {
      "affs": [
        9
      ],
      "name": "Sanjay Goel",
      "orcid": "0000-0002-2798-7568"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/11skkqp65yf9t.bib",
  "cited_by": 0,
  "doi": "10.1158/1078-0432.ccr-26-1076",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725326/",
  "id": "11skkqp65yf9t",
  "issns": [
    "1078-0432",
    "1557-3265"
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  "landing_url": "https://doi.org/10.1158/1078-0432.ccr-26-1076",
  "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/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomarkers"
    ],
    [
      "heading",
      "Breast Cancer"
    ],
    [
      "heading",
      "Clinical Trial Results"
    ],
    [
      "heading",
      "Clinical Trials: Novel Mechanisms"
    ],
    [
      "heading",
      "Gastrointestinal Cancers"
    ],
    [
      "heading",
      "Gynecological Cancers"
    ],
    [
      "heading",
      "Phase II clinical trials"
    ],
    [
      "heading",
      "Small Molecule Agents"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7170196843",
  "pdf_url": null,
  "pmcid": "PMC13725326",
  "pmid": "42489683",
  "published": "2026-07-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/11skkqp65yf9t.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:23:44Z",
      "native_id": "PMC13725326",
      "source": "pmc",
      "url": "https://doi.org/10.1158/1078-0432.ccr-26-1076"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
    }
  ],
  "title": "Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial",
  "title_text": "Multikinase Inhibition with Tinengotinib in Advanced Solid Tumors: Results from a Multicenter Phase Ib/II Trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:21:56Z",
  "url": "https://research.draconitic.com/paper/11skkqp65yf9t",
  "venue": "Clinical Cancer Research",
  "versions": []
}