MIV-818 is being developed for patients with hepatocellular carcinoma (HCC). HCC represents the fifth most common cancer worldwide1) but is a rare disease in Europe and the US. MIV-818 has received a positive opinion on orphan medicinal drug designation by EMA and has been granted orphan drug designation by the FDA for the treatment of HCC.
1) Childs A. et al., Chin Clin Oncol;2(4):44; 2013
MIV-818 is being developed as an orally administrated drug for the treatment of primary liver cancer. The intention is to achieve maximum concentration of the active substance in the liver, while minimizing the levels of the active substance in the rest of the body to reduce the risk of side effects. MIV-818 has the potential to be the first liver cancer-targeted and orally administered drug that can help patients with HCC and other forms of liver cancer.
The phase 1 study of MIV-818 consists of two parts: a phase 1a study in which individual patients receive escalating doses of MIV-818 and a phase 1b study in which the dose is escalated in cohorts of three patients in a 3+3 design to identify the recommended phase 2 dose (RP2D). The purpose of this first-in-human trial is to study the safety, tolerability, pharmacokinetics, pharmacodynamics, and signs of antitumor effect of MIV-818 in patients with advanced liver cancer. It will enroll patients with hepatocellular carcinoma (HCC), as well as patients with intrahepatic cholangiocarcinoma and patients with liver metastases from solid tumors.
The phase 1a study has been completed and the last patient in phase 1b has been recruited. Evaluated doses in phase 1a and 1b were generally well-tolerated by patients. Liver biopsies showed selective DNA damage in liver tumor tissue while normal liver tissue was minimally or not affected by the treatment. From the patient biopsies we also observed DNA damage in oxygen-poor cancer tissue, which are generally difficult to treat. The tumor selective DNA damage effect was observed at low plasma concentrations of MIV-818 and acceptable exposure to troxacitabine in plasma.
The next step in the development of MIV-818 is a phase I/2a combination study, where MIV-818 will be administered either with lenvatinib, a tyrosine kinase inhibitor or pembrolizumab, an anti-PD-1 check-point inhibitor. The planned trial will be an open-label, multi-center, dose escalation/expansion study to establish the RP2D as well as initial evaluation of the safety and efficacy of the combination of MIV-818 with lenvatinib or pembrolizumab. The study will include patients with HCC who have progressed on, or are intolerant of, first line standard therapy.
The study is planned to have two parallel dose-escalation streams. Once the RP2D has been established for the combinations, further cohorts of up to 30 patients with HCC will be enrolled in the phase 2a part of the study. The first patient is expected to be enrolled in the second half of 2021.