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First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors

Abstract: This first-in-human, phase I clinical trial was designed to determine the dose-limiting toxicities (DLTs) and the dose for phase II trials (P2D) of elisidepsin (PM02734) administered as a 30-min or as a 3-h intravenous infusion every 3 weeks (q3wk). Between March 2006 and April 2011, 53 patients with advanced malignant solid tumors were enrolled and treated with elisidepsin on the two different q3wk infusion schedules: 22 (30-min) and 31 (3-h), respectively. Doses evaluated ranged from 0.1 to 1.6 mg/m2 (30-min q3wk) and from 2.0 to 11.0 mg flat dose (FD) (3-h q3wk). In the 30-min q3wk schedule, transient grade 3/4 increases in hepatic transaminases were the DLT, which appeared at the highest doses tested (from 1.1 to 1.6 mg/m2). No DLTs were observed on the 3-h schedule at doses up to 11.0 mg q3wk. Common adverse events were grade 1/2 pruritus, nausea, fatigue and hypersensitivity. Of note, myelotoxicity was not observed. Plasma maximum concentration and total drug exposure increased linearly with dose. Prolonged (≥3 months) disease stabilization was observed in pretreated patients with pleural mesothelioma (n = 1) in the 30-min q3wk arm, and with colorectal adenocarcinoma (n = 3), esophagus adenocarcinoma, endometrium adenocarcinoma, pleural mesothelioma, and head and neck carcinoma (n = 1 each) in the 3-h q3wk arm. In conclusion, elisidepsin doses of 1.1 mg/m2 (equivalent to a FD of 2.0 mg) and 11.0 mg FD are the dose levels achieved for further phase II trials testing the 30-min q3wk and 3-h q3wk schedules, respectively.

Full Reference: Ratain, Mark J., David Geary, Samir D. Undevia, Cinthya Coronado, Vicente Alfaro, Jorge L. Iglesias, Richard L. Schilsky, and Bernardo Miguel-Lillo. “First-in-Human, Phase I Study of Elisidepsin (PM02734) Administered as a 30-Min or as a 3-Hour Intravenous Infusion Every Three Weeks in Patients with Advanced Solid Tumors.” Investigational New Drugs 33, no. 4 (August 2015): 901–10. doi:10.1007/s10637-015-0247-1.

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