1. Phase I first-in-human study of the PI3 kinase inhibitor GSK2126458 (GSK458) in patients with advanced solid tumors (study P3K112826)
- Author
-
Thomas A. Lampkin, J.H.M. Schellens, Adil Daud, Elizabeth Claire Dees, Jennifer M. Specht, E. Y. Yu, E. E. Voest, Gerald Steven Falchook, Martijn P. Lolkema, Emily K. Bergsland, Shannon R. Morris, R. Kurzrock, Deborah A. Smith, Juneko E. Grilley-Olson, Sheng-Bin Peng, Siquing Fu, Joseph F. Kleha, Antoinette R. Tan, Pamela N. Munster, and R. van der Noll
- Subjects
Cancer Research ,Kinase ,business.industry ,Cmax ,Pharmacology ,Oncology ,Pharmacokinetics ,Refractory ,In vivo ,Pharmacodynamics ,Toxicity ,Cancer cell ,Medicine ,business - Abstract
3018 Background: Phosphatidylinositol 3-kinase (PI3K) is critical to cancer cell growth, survival, and metabolism. GSK458 is an oral, potent inhibitor of PI3K (α, β, γ, δ), mTORC1, and mTORC2. Preclinically, GSK458 has demonstrated broad anti-tumor activity against solid tumors and hematologic malignancies in vitro and in vivo. Cell lines with common activating mutations of PIK3CA are particularly sensitive to GSK458. Methods: Adult patients (pts) with relapsed or refractory advanced solid tumors received GSK458 by mouth daily until disease progression or toxicity. Dose escalation used a modified accelerated titration scheme. Expansion cohorts further evaluated pharmacodynamics (PD), pharmacokinetics and clinical activity in specific target populations. Results: Preliminary data reveal that 78 pts (51% female) with mean age of 57 (25-85) yrs received ≥1 dose of GSK458. Doses ranged from 0.1 to 3 mg. Maximum tolerated dose was 2.5 mg daily. AUC and Cmax increased with dose. Across doses: median Tmax was 2 ...
- Published
- 2011
- Full Text
- View/download PDF