Liver cancer is the fourth highest cause of cancer-related death worldwide1). MIV-818 is developed for patients with advanced liver cancers for whom existing treatment options provide very little survival benefit.
1) Globocan 2018
Although existing therapies for advanced hepatocellular carcinoma (HCC) are capable of extending the lives of patients with HCC, treatment benefits are low while death rates remain high. HCC is a very diverse disease with multiple cancer cell types and without specific mutations seen in other tumor types. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.
Intrahepatic cholangiocarcinoma, a cancer of the bile duct located inside the liver tissue, accounts for about 15 percent of liver cancers. It has a poor prognosis and no treatment that effectively improves survival. Liver metastases from other tumor sites (principally from colorectal cancer, but also from breast, ovarian and pancreatic cancer) are also a major cause of cancer-related death.
MIV-818, the first oncology drug in development from Medivir’s in-house research, has been specifically designed for liver cancers both in its delivery to the liver and in its way of acting, aimed to make it more effective against liver cancer cells specifically. It has the potential to become the first liver-targeted, orally administered drug to benefit patients with HCC and other forms of liver cancer.
MIV-818 is a liver-targeted nucleotide prodrug of troxacitabine. It has been developed to be an orally administered therapeutic with a high level of anti-tumor activity that is targeted for delivery to the liver. The intention is to maximize delivery of the drug to the tumor or tumors, while minimizing the systemic toxicity. The objective is to improve the anti-tumor effect while simultaneously reducing potential side effects.
The purpose of this first-in-human trial is to study the safety, tolerability, pharmacokinetics, and preliminary antitumor activity 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 design of phase I/II study of MIV-818 consists of three parts: a phase Ia study in which individual patients receive escalating doses of MIV-818. This will be followed by a phase Ib study in which the dose is escalated in cohorts of three patients in a 3+3 design in order to identify the recommended phase II dose (RP2D), which will be determined by the trial’s independent safety review committee. In the third and final part of the study two dose expansion cohorts of patients, one with HCC and the other with intrahepatic cholangiocarcinoma, will receive MIV-818 at the RP2D.
The regulatory application to conduct the study was first reviewed and approved by the United Kingdom Medicinal and Healthcare Products Regulatory Agency (MHRA), and the phase Ia part of the trial will be run at sites in the United Kingdom and Belgium.
Unmet medical need
Limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC.
MIV-818 is a nucleoside pro-drug delivering its active metabolite via oral administration to cancers in the liver while increasing the therapeutic window.
Clinical phase I/II study