Aim: To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer.Materials & methods: 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.Results: The drug exposure levels in the phase I trial were determined by the in vivo 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.Conclusion: The drug was safe and tolerable in patients with advanced liver cancer.Clinical Trial Registration: ChiCTR2100044235 (www.chictr.org.cn).
Keywords: CT102; IGF-1R; antisense oligonucleotide; liver cancer; pharmacokinetics; targeted therapy.
CT102 is a potential new drug for liver cancer treatment. It belongs to a new form of medicine using gene therapy technology called antisense oligonucleotides. There are some antisense oligonucleotides approved for treating rare diseases. This study evaluated the antitumor effect, metabolism and safety of CT102 in preclinical and clinical trials. The results showed that CT102 could inhibit tumor growth in mice with liver cancer and maintain high levels in the liver. It was found that CT102 was safe and tolerable in patients with advanced liver cancer. This suggests that CT102 has therapeutic potential for liver cancer treatment. The good tolerability and safety of CT102 in patients supports further studies on liver cancer treatment.