Background: MGCD516, is an orally-available, potent small molecule inhibitor of a closely related family of RTKs including RET, TRK family, DDR2, MET, Axl family, KIT, as well as VEGFR and PDGFR family members. RTKs inhibited by MGCD516 are genetically altered in a variety of cancers, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), functioning as oncogenic drivers promoting cancer development and progression. Alterations in these RTKs have also been implicated in tumor resistance mechanisms. MGCD516 has demonstrated broad antitumor activity including demonstration of tumor regression in preclinical models harboring genetic dysregulation of MGCD516 targets including MET amplification, METex14del, RET rearrangement and CHR4q12 amplification. Methods: This first-in-human, open label Phase 1/1b study is designed to evaluate the safety, pharmacokinetics, metabolism, pharmacodynamics and clinical activity of MGCD516 in patients with advanced solid tumors. Phase 1 is the dose escalation phase and uses the modified toxicity probability interval (mTPI) method to determine the MTD /Recommended Phase 1b Dose. Phase 1b is the expansion phase in which MGCD516 will be evaluated in patients with NSCLC, HNSCC, or any other solid tumor type harboring specific MGCD516 RTK target mutations of interest. Phase 1 and 1b are each anticipated to enroll 60 patients. Phase 1 enrollment started in September 2014, with patients receiving continuous daily dosing (QD) of 10mg MGCD516 in cycles of 21 days. Cohort 1 and Cohort 2 (QD 20mg) have been completed without DLTs and enrollment to Cohort 3 (QD 40mg) started in January 2015. Pharmacokinetics is evaluated after single and repeated administration. Pharmacodynamic biomarkers, including soluble (s)MET, sVEGFR2 and VEGFA will be explored in plasma samples for prognostic potential and possible relationship with clinical outcome. Clinical trial information: NCT02219711