{
  "abstract": "PURPOSE: Pancreatic adenocarcinoma is a devastating disease for which there are limited treatment options. Identification of novel agents to enhance the activity of existing regimens is much needed. We hypothesized that the disruption of the DNA damage response by AZD1775, an oral Wee1 inhibitor, added to the nab-paclitaxel and gemcitabine chemotherapy backbone would be safe and effective. METHODS: A phase I trial to evaluate the dose-limiting toxicities and maximum tolerated dose of AZD1775 in combination with nab-paclitaxel and gemcitabine was conducted in patients with metastatic or locally advanced, unresectable pancreatic adenocarcinoma (NCT02194829). A total of 7 patients received nab-paclitaxel and gemcitabine intravenously on days 1, 8, and 15 of a 28-day treatment cycle, along with AZD1775 by mouth on days 1, 2, 8, 9, 15, and 16. Toxicities were assessed using CTCAE version 4 criteria. RESULTS: Two patients were treated at the initial dose level of nab-paclitaxel, gemcitabine, and AZD1775, and both experienced dose-limiting toxicities (dehydration, elevated bilirubin, oral mucositis, increased AST, and Candida intertrigo). Under a revised study design, 5 patients were treated, and 2 of them also developed dose-limiting toxicities (anemia, thrombocytopenia, neutropenia, hyponatremia, and febrile neutropenia). Progression-free survival (PFS) and overall survival (OS) among these 7 patients were 5.26 months (95% confidence interval [CI] [2.73, 12.16]) and 5.29 months (95% CI [2.73, 20.17]), respectively. CONCLUSION: The combination of nab-paclitaxel, gemcitabine, and AZD1775 was determined to be too toxic when administered in patients with metastatic or locally advanced, unresectable pancreatic adenocarcinoma.",
  "abstract_shown": true,
  "affiliations": [
    "University of Pennsylvania, Abramson Cancer Center, 3400 Civic Center Blvd, South Pavilion 10 Floor, Philadelphia, PA, 19104, USA.",
    "Dana-Farber Cancer Institute, Department of Data Science, 450 Brookline Ave, Boston, MA, 02215, USA.",
    "National University Cancer Institute, Singapore, National University Health System, Singapore.",
    "Case Western Reserve University, Case Comprehensive Cancer Center, 2103 Cornell Road, Cleveland, OH, 44106, USA",
    "Current Affiliation: Neal Meropol, LLC, USA.",
    "Northwestern University, 541 N. Fairbanks Ct, Suite 2300, Chicago, IL, 60611, USA.",
    "Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA",
    "Current Affiliation: Penn Medicine, Ann B. Barshinger Cancer Center, Lancaster General Health, 2102 Harrisburg Pike, Lancaster, PA.",
    "Vanderbilt-Ingram Cancer Center, 2220 Pierce Ave, Nashville, TN, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jennifer R. Eads"
    },
    {
      "affs": [
        1
      ],
      "name": "Ju-Whei Lee"
    },
    {
      "affs": [
        2
      ],
      "name": "Cheng E. Chee"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Neal J. Meropol"
    },
    {
      "affs": [
        5
      ],
      "name": "Al B. Benson"
    },
    {
      "affs": [
        1
      ],
      "name": "Paul Catalano"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Efrat Dotan"
    },
    {
      "affs": [
        8
      ],
      "name": "Dana B. Cardin"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter J. O’Dwyer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6jfj6s8r8hyzc.bib",
  "cited_by": 0,
  "doi": "10.1016/j.clcc.2026.08.004",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714758/",
  "id": "6jfj6s8r8hyzc",
  "issns": [
    "1533-0028",
    "1938-0674"
  ],
  "landing_url": "https://doi.org/10.1016/j.clcc.2026.08.004",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7206178863",
  "pdf_url": null,
  "pmcid": "PMC13714758",
  "pmid": "42763280",
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6jfj6s8r8hyzc.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:11Z",
      "native_id": "PMC13714758",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.clcc.2026.08.004"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "A Phase I Study of Nab-Paclitaxel, Gemcitabine and AZD1775 for Treatment of Metastatic Adenocarcinoma of the Pancreas: ECOG-ACRIN EA2131",
  "title_text": "A Phase I Study of Nab-Paclitaxel, Gemcitabine and AZD1775 for Treatment of Metastatic Adenocarcinoma of the Pancreas: ECOG-ACRIN EA2131",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:11Z",
  "url": "https://research.draconitic.com/paper/6jfj6s8r8hyzc",
  "venue": "Clinical colorectal cancer",
  "versions": []
}