|The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2021 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
MIV-818, a nucleoside analogue prodrug, induced antitumor activity with an acceptable safety profile in patients with hepatocellular carcinoma (HCC), hepatic cholangiocarcinoma (CCA), or liver metastases from solid tumors, according to the results of a phase 1a study presented at the 2021 Gastrointestinal Cancers Symposium.
Because MIV-818 is a prodrug, its conversion to the nucleoside analogue troxacitabine in the liver results in liver-targeted DNA breaks and ultimately, cell death. The aim of this phase 1a study was to determine the safety and efficacy of investigational agent, as well as an optimal dose.
Investigators of the phase 1a study (ClinicalTrials.gov identifier: NCT03781934) treated 9 patients (2 with advanced HCC, 1 with CCA, and 6 with liver metastases) with MIV-818 at doses up to 60 mg. All patients had received prior treatment for their disease.
Primary end points included safety and tolerability and establishing the starting dose for the inter-patient dose-escalation phase 1b study. Secondary objectives included overall response rate (ORR) and pharmacokinetic and dynamic effects.
At baseline, the median age of patients was 57 years (range, 50-84). Patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median number of lines of prior therapies was 2 (range, 1-5).
Preliminary data indicated that MIV-818 was delivered to the liver with low plasma levels. DNA damage was observed in tumor cells of liver biopsies, suggesting “clear signs of a tumor-selective effect,” according to T.R. Jeffry Evans, FRCP, MBBS, MD, who presented the findings. Additional efficacy outcomes were not reported.
The majority of treatment-related adverse events (AEs) were grade 1 at doses below 50 mg. Nausea, elevations in liver enzymes, and fatigue were among the most common AEs. Hematologic AEs were observed with doses of 50 mg or higher.
The starting dose selected for the ongoing phase 1b trial was 40 mg. To date, 1 dose-limiting toxicity of rash has been observed in the phase 1b setting, which resolved with a dose reduction to 30 mg.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Medivir AB, Sweden.
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Evans TRJ, Cutsem EV, Prenen H, et al. Phase I study of the novel pro-drug MIV-818 in patients with hepatocellular carcinoma, intra-hepatic cholangiocarcinoma or liver metastases. Presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 309.