Safety, pharmacokinetics, and pharmacodynamics results from a phase I trial of BAY 86-9766 (RDEA119), a MEK inhibitor, in patients with advanced cancer.

• DOI: 10.1200/jco.2011.29.15_suppl.3007
• Publication Date: 2017-02-23T18:58:03Z
• Authors: L. Gore; K. Lewis; D. D. Von Hoff; G. J. Weiss; R. K. Ramanathan; A. A. Adjei; G. K. Dy; W. W. Ma; N. J. Clendeninn; D. P. Leffingwell; B. Sheedy; C. Iverson; J. N. Miner; Z. Shen; L. Yeh; R. L. Dubowy; M. Jeffers; P. Rajagopalan; C. D. Weekes
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

3007 Background: BAY 86-9766 is a highly selective, allosteric inhibitor of MEK1/2. A phase I dose-escalation trial was conducted to determine the maximum tolerated dose (MTD), pharmacokinetics (PK) and pharmacodynamics (PD) in patients with advanced metastatic or locally recurrent solid tumors. Methods: Sixty-nine patients received doses from 2-160 mg once daily (QD) or 50-80 mg twice daily (BID). Tumor types included 22 colorectal (CRC), 8 melanoma, 5 prostate, 5 NSCLC, 5 pancreatic, 3 adrenal, 3 cholangiocarcinoma, 2 breast and 16 other. Patients were given a single oral dose on Day 1, were off drug for 7 days, and then began a 28-day course of daily continuous dosing. If benefiting, dosing continued in 28-day courses with tumor response and PD assessed every 2 courses. Safety was assessed by adverse events (AEs), clinical laboratory tests, vital signs, ECGs, ECHO/MUGA scans and physical exams. PK was collected each course. PD assessments included circulating tumor cells, leukocyte phosphorylated ERK (...