A Phase I Study of Nab-Paclitaxel, Gemcitabine and AZD1775 for Treatment of Metastatic Adenocarcinoma of the Pancreas: ECOG-ACRIN EA2131
Year: 2026
Type: article
Study design: Clinical Trial
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.
Source: Clinical Colorectal Cancer
Institutions: Abramson Cancer Center, University of Pennsylvania, Dana-Farber Cancer Institute, National University Cancer Institute, Singapore, National University Health System, Case Comprehensive Cancer Center, Case Western Reserve University, Northwestern University, Fox Chase Cancer Center, Lancaster General Hospital, University of Pennsylvania Health System, Vanderbilt University, Vanderbilt-Ingram Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, American College of Radiology Imaging Network, Celgene, Boston Scientific Corporation, Les Laboratories Pierre Fabre, National Comprehensive Cancer Network, Incyte, ECOG-ACRIN Cancer Research Group, Association of Community Cancer Centers, Syndax Pharmaceuticals, Flatiron Health, Natera, Astellas Pharma, Ipsen, Aptitude Health, National Institutes of Health, Genentech, Samsung, Pharmacyclics, National Cancer Institute
Awards: ECOG-ACRIN Network Group Operations Center, G2819266960, Northwestern University Lead Academic Participating Site, NCI National Clinical Trials Network (UG1), G5782779775, G6317847318, G6648927030, G6705915398, ECOG-ACRIN Network Group Statistics and Data Management Center, Case Comprehensive Cancer Center NCTN Lead Academic Participating Site, G8220656038, Vanderbilt Network Lead Academic Participating Site for the NCTN, G993993821
OpenAlex ID: W7206178863