Study of Fostrox Plus Lenvatinib in HCC Advances to Phase 2a

The initial dose-escalation portion of a phase 1b/2a study (NCT03781934) evaluating fostroxacitabine bralpamide (fostrox; MIV-818) in combination with lenvatinib (Lenvima) for the treatment of patients with hepatocellular carcinoma (HCC) was successfully completed with the recommended phase 2 dose determined (RP2D), according to Medivir AB.¹

According to the preliminary results from the dose cohorts, the RP2D for the first combination arm of phase 2a is 30 mg for fostrox. Additionally, the combination had a good safety and tolerability profile and there were no dose-limiting toxicities observed.

Fostrox works to selectively treat liver cancer and lessen the side effects associated with liver cancer. Previously in May 2020, the FDA granted an orphan drug designation to fostrox, the novel liver-targeted drug, for the treatment of patients with HCC.

“It is very satisfactory that we have now completed the first part of the study with good preliminary results and have been able to determine the starting dose for the first combination arm in the phase 2a part of the study. With the great interest we have seen in the study, it is also gratifying for the patients that we can now start the first combination arm in the phase 2a part," stated Jens Lindberg, chief executive officer at Medivir AB, in the press release. "Although Lenvima is now widely used as a second-line treatment for advanced HCC, there is still a need to improve the number of patients who respond to the treatment. By using fostrox in addition to [lenvatinib], our hope is that more of these patients will obtain a clinical response to their treatment."

The open-label, multi-center study is evaluating the combination of fostrox with either lenvatinib, a tyrosine kinase inhibitor, or the anti-PD-1 checkpoint inhibitor pembrolizumab (Keytruda).²

Patients aged 18 years and older with HCC for whom current first-line treatment has shown to be ineffective or intolerable are being enrolled in the trial if they have measurable disease based on RECIST v1.1, a Child-Pugh A status for phase 1a and a Child-Pugh A or B status for phase 1b and 2a, an ECOG performance status of 0 or 1 at the time of screening,life expectancy of greater than 12 weeks, and more.

Investigators are evaluating the primary end points of incidence and severity of adverse events, the incidence and magnitude of changes in red blood cell count, white blood cell count, platelet count, aspartate aminotransferase, alanine aminotransferase, bilirubin, and vital signs that are clinically significant. Vital signs being evaluated include systolic and diastolic blood pressure, pulse rate, body temperature, and weight. Secondary end points of the study include preliminary efficacy determined by RECIST evaluation and plasma levels of α fetoprotein.

Overall, the main goal of the trial is to assess the safety and tolerability of the combination of fostrox with lenvatinib or pembrolizumab in patients with HCC. Investigators will also be looking to get an indication of the efficacy of fostrox in combination with these 2 agents.

Phase 2a, the dose-expansion portion of the study, will enroll up to 30 more patients with HCC to assess the safety and efficacy of the combination. The study is being conducted at 14 locations across the United Kingdom, Spain, and South Korea.

The phase 1b dose-escalation portion evaluating fostrox with pembrolizumab is currently ongoing and 6 patients are on active treatment in the study.

REFERENCES:

Medivir has determined the recommended phase 2 dose for fostrox in combination with Lenvima in HCC. News release. Medivir AB. February 20, 2023. Accessed February 21, 2023. https://prn.to/3SgqZqV

A study to evaluate MIV-818 in patients with liver cancer manifestations. ClinicalTrials.gov. Accessed February 2023. Updated November 14, 2022. https://clinicaltrials.gov/ct2/show/NCT03781934?term=fostroxacitabine+bralpamide&draw=2&rank=1