First-in-human trial of the PI3K[beta]-selective inhibitor SAR260301 in patients with advanced solid tumors

• Published in: Cancer Vol. 124; no. 2; p. 315
• Main Authors: Bedard, Philippe L, Davies, Michael A, Kopetz, Scott, Juric, Dejan, Shapiro, Geoffrey I, Luke, Jason J, Spreafico, Anna, Wu, Bin, Castell, Christelle, Gomez, Corinne, Cartot-Cotton, Sylvaine, Mazuir, Florent, Dubar, Michel, Micallef, Sandrine, Demers, Brigitte, Flaherty, Keith T
• Format: Journal Article
• Language: English
• Published: Atlanta Wiley Subscription Services, Inc 01.01.2018
• Subjects: 1-Phosphatidylinositol 3-kinase; Anticancer properties; Antitumor activity; Bayesian analysis; Cancer; Constraining; Diarrhea; Drug development; Enzyme inhibitors; Exposure; Homology; Inhibitors; Mathematical models; Nausea; Oncology; Overdose; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology; Platelets; Pneumonitis; PTEN protein; Quality; Safety; Solid tumors; Tensin; Toxicity; Tumors; Vomiting

BACKGROUND Phosphoinositide 3-kinase (PI3K) [beta] is the dominant isoform for PI3K activity in many phosphatase and tensin homolog (PTEN)-deficient tumor models. This was a first-in-human study to determine the maximum tolerated dose, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary...