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This study characterized the pharmacokinetics, mass balance, routes and extent of elimination, metabolites, and safety of a single oral dose of 14C-linsitinib, an IGF-1R/IR inhibitor, in patients with advanced solid tumors. The tolerability of linsitinib after multiple-dose administration was assessed in those patients who wished to continue treatment beyond the single 14C-linsitinib dose. Five patients received a single oral dose of 150 mg 14C-linsitinib, followed by collection of blood, plasma, urine, and feces for 10 days. The collected material was analyzed for total radioactivity, linsitinib, and metabolites. The safety of 150 mg of unlabeled linsitinib administered twice daily until disease progression was also assessed. The median time to reach the maximum plasma concentration of linsitinib was 3.0 h, median maximum plasma concentration was 1789 ng/mL, median terminal half-life was 2.4 h, and median apparent oral clearance was 12.45 L/h. After a single dose of 14C-linsitinib, 5.44 and 76.4 % of mean total radioactivity administered were recovered in urine and feces, respectively. Eighteen linsitinib metabolites (M1–M18) were detected in plasma, urine, and feces samples, and their structures were elucidated. The main metabolic reactions of linsitinib in humans were oxidation and sulfate conjugation. Linsitinib was well tolerated after a single dose of 14C-linsitinib, and fatigue was the most frequent adverse event following multiple doses of unlabeled linsitinib. 14C-linsitinib is rapidly absorbed and extensively metabolized. Linsitinib excretion via bile into feces is the predominant elimination route from plasma with minor renal elimination.