Preclinical and phase I studies of an antisense oligonucleotide drug targeting in liver cancer.

To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer. The tolerability and safety of an investigational new drug were evaluated in a dose-escalation trial involving 17 patients with advanced liver cancer after preclinical assessment of pharmacokinetics and pharmacodynamics. The drug exposure levels in the phase I trial were determined by the efficacy with pharmacokinetics evaluation in rats and rhesus monkeys. This clinical study showed that the maximum tolerated dose was 3.96 mg/kg, and the dose-limiting toxicity dose was 4.4 mg/kg. The drug was safe and tolerable in patients with advanced liver cancer. ChiCTR2100044235 (www.chictr.org.cn).