Phase I clinical trial of KML001 monotherapy in patients with advanced solid tumors

• Published in: Expert opinion on investigational drugs Vol. 29; no. 9; p. 1059
• Main Authors: Kim, Seokuee, Kim, Sujong, Park, Young Suk, Park, Joon Oh, Lim, Ho Yeong, Ahn, Jin Seok, Lee, Jeeyun, Sun, Jong Mu, Kang, Won Ki, Han, RaeO, Kim, Jungryul, Ahn, Myung-Ju
• Format: Journal Article
• Language: English
• Published: England 01.09.2020
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Arsenites - administration & dosage; Arsenites - adverse effects; Arsenites - pharmacokinetics; Disease Progression; Dose-Response Relationship, Drug; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms - drug therapy; Neoplasms - pathology; Sodium Compounds - administration & dosage; Sodium Compounds - adverse effects; Sodium Compounds - pharmacokinetics; Treatment Outcome; arsenical; Anticancer; KML001; monotherapy; telomere
• ISSN: 1744-7658
• DOI: 10.1080/13543784.2020.1804855

We evaluated the tolerability, pharmacokinetics (PK) and preliminary efficacy of KML001, an oral trivalent arsenical, as a monotherapy in patients with advanced solid tumors. With a standard 3 + 3 design for dose-escalation stage, the planned dose levels of KML001 were 5, 7.5, 10, 12.5, and 15 mg/day for 28 days. Once the maximum tolerated dose was determined, 22 subjects were additionally enrolled for dose-expansion stage. PK analysis was performed in the 5, 10, and 15 mg/day cohort at the dose-escalation stage and also at the dose-expansion stage. Moreover, response was assessed using the standard RECIST 1.1. A total of 45 Korean subjects were enrolled. No DLT was reported at the dose-escalation stage. Three DLTs, two cases of prolonged QTc interval and one of neutropenia, were reported in the 12.5 mg/day cohort at the dose-expansion stage. Higher total daily doses up to 12.5 mg/day of KML001 resulted in higher trough plasma concentrations. Among the 18 subjects who completed 2 cycles of therapy, 15 had progressive disease and 3 had stable disease. Doses equal to or greater than 10 mg/day KML001 alone were tolerable and produced plasma concentrations higher than biologically relevant targets.