A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer

• Published in: Investigational new drugs Vol. 33; no. 3; pp. 710 - 719
• Main Authors: Azaro, Analia, Rodon, Jordi, Calles, Antonio, Braña, Irene, Hidalgo, Manuel, Lopez-Casas, Pedro P., Munoz, Manuel, Westwood, Paul, Miller, Joel, Moser, Brian A., Ohnmacht, Ute, Bumgardner, William, Benhadji, Karim A., Calvo, Emiliano
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2015; Springer Nature B.V
• Subjects: Adult; Aged; AKT protein; Alanine; Alanine transaminase; Anemia; Animals; Anticancer properties; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Antitumor activity; Aspartate aminotransferase; Biopsy; Cancer; Cancer therapies; Cell cycle; Cell growth; Constipation; Diarrhea; Drug dosages; Enzyme inhibitors; Epidermis; Female; Health services; Humans; International; Kinases; Male; Medical research; Medicine; Medicine & Public Health; Metabolites; Metastases; Metastasis; Mice, Nude; Middle Aged; Nausea; Neoplasm Metastasis; Neoplasm Staging; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - pathology; Neutropenia; Oncology; p70 S6 kinase; Patients; Pharmaceutical industry; Pharmacodynamics; Pharmacokinetics; Pharmacology; Pharmacology/Toxicology; Phase I Studies; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - therapeutic use; Proteins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; R&D; Regulatory approval; Research & development; Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Skin; Studies; Toxicity; Transaminases; Tumors; Xenograft Model Antitumor Assays; Young Adult; γ-Glutamyltransferase; Spain; PI3K/Akt/mTOR signaling pathway; mTOR; p70 S6 kinase (p70S6K); Akt; LY2780301; Cancer

Summary The primary objective of this phase I study of LY2780301, a dual p70 S6 kinase and Akt inhibitor, was to determine the recommended phase II dose as a single agent in patients with advanced cancer. Secondary objectives included safety, pharmacokinetic, and pharmacodynamic analyses, and co-cli...