CD-801

CD-801 is a novel therapeutic agent being developed for liver cancer, specifically hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is a lipid nanoparticle-encapsulated self-replicating RNA that encodes hepatocyte nuclear factor 4α (HNF4α)[1][8]. This drug is designed to enhance the expression of HNF4α and selectively target liver cancer cells[2][5]. ## Mechanism of Action CD-801 works through a differentiation therapy approach. HNF4α plays a critical role in hepatocarcinogenesis, and restoring its expression induces the differentiation of HCC cells into mature hepatocytes[2]. Preclinical studies have demonstrated that CD-801 effectively inhibits the growth of subcutaneous and orthotopic liver tumors in mice[2][6]. ## Clinical Development Currently, CD-801 is in early phase 1 clinical trials for both advanced hepatocellular carcinoma and advanced intrahepatic cholangiocarcinoma[1][8]. These trials are being sponsored by Shanghai Changzheng Hospital[1][5]. The drug is being administered through different routes in various trials: - Intravenous administration for HCC treatment[3][5][9] - Transarterial (hepatic arterial) injection for both HCC and ICC[1][2][8] ## Dosing Information The clinical trials are exploring various dosing regimens: - Dose escalation phase testing 25 μg, 50 μg, and 100 μg doses[5] - Treatment schedule typically involves a second dose 14 ± 3 days after initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments based on patient tolerance and therapeutic response[5][9] - For hepatic arterial injection, 100 μg of CD-801 is administered every 14 ± 3 days[1][2] ## Safety Profile Preclinical acute toxicity tests in Sprague-Dawley rats have shown that a single intravenous injection of CD-801 at a dose of 150 μg/animal is well-tolerated, with no significant toxicity[2][6]. In the dose escalation phase of a completed clinical trial, CD-801 at doses of 25, 50, and 100 μg was found to be well-tolerated with no dose-limiting toxicities during the DLT phase[2]. The ongoing clinical trials aim to further evaluate the safety, tolerability, and efficacy of CD-801 in patients with advanced liver cancers.