التفاصيل البيبلوغرافية
| العنوان: |
First-in-human study of the anti-HB-EGF antibody U3-1565 in subjects with advanced solid tumors. |
| المؤلفون: |
Moore, Kathleen N., Bendell, Johanna C., LoRusso, Patricia M., Olszanski, Anthony J., Zwick-Wallasch, Esther, Jansen, Mendel, Vandell, Alexander G., Senaldi, Giorgio |
| المصدر: |
Investigational New Drugs; Feb2019, Vol. 37 Issue 1, p147-158, 12p |
| مصطلحات موضوعية: |
THERAPEUTIC use of monoclonal antibodies, ANTINEOPLASTIC agents, CELL lines, CLINICAL trials, COLON tumors, DRUG tolerance, DRUG side effects, CLINICAL drug trials, EXANTHEMA, FATIGUE (Physiology), GROWTH factors, LONGITUDINAL method, METASTASIS, MONOCLONAL antibodies, RECTUM tumors, TUMORS, VASCULAR endothelial growth factors, TREATMENT effectiveness, SEVERITY of illness index, TUMOR grading |
| مستخلص: |
U3-1565 is a monoclonal antibody directed against heparin-binding epidermal growth factor-like growth factor (HB-EGF), which mediates angiogenesis via induction of vascular endothelial growth factor (VEGF-A). This first-in-human study characterized the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of U3-1565 in subjects with advanced solid tumors. In Part 1 (dose escalation following a modified 3 + 3 design), Cohorts 1-4, U3-1565 was administered at 2, 8, 16, and 24 mg/kg every 3 weeks for Cycle 1 and every 2 weeks thereafter. In Part 1, Cohort 5, and in Part 2 (dose expansion), U3-1565 was administered at 24 mg/kg every week. Thirty-six subjects were enrolled and treated (15 in Part 1; 21 in Part 2). No subject experienced dose limiting toxicity and maximum tolerated dose was not reached. All drug-related events were Grade 1 or 2 in severity, with fatigue and rash predominating. Following treatment with U3-1565, 1 subject with metastatic colorectal cancer experienced partial response and 6 subjects achieved stable disease. Four subjects completed the study main phase (first 12 cycles) and entered the extension phase. Of the 6/36 subjects with high (> 1500 pg/ml) baseline VEGF-A levels, all showed a decrease in VEGF-A (median − 60% [−22% to −97%]). Of the remaining subjects, only 19/30 showed a decrease (median − 18% [−2% to −82%]). Subjects with high VEGF-A baseline levels remained on treatment longer (3/6 entered study extension phase versus 1/30), and were more likely to show disease control (3/6 versus 4/30). In conclusion, U3-1565 demonstrates both proof of mechanism and clinical activity across different tumor types. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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