Phase 1b/2a Study of Fostrox Completes Dose-Escalation Portion in HCC

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A safe dose of fostroxacitabine bralpamide (fostrox; MIV-818) has been established in the completed phase 1b, dose-escalation portion of a phase 1b/2a study, evaluating the agent in combination with pembrolizumab (Keytruda) for patients with hepatocellular carcinoma (HCC).¹

With a safe dose determined for the fostrox and pembrolizumab arm, experts will explore the possibility of fostrox as a triplet combination in earlier lines of immunotherapy combinations.

The ongoing expansion portion, phase 2a, will now evaluate the combination of fostrox with levnantinib (Lenvima) using the recommended dose from the first portion of the study.

"It is very gratifying that we have now completed the dose-escalation part for both dose arms and established a safe dose," said Pia Baumann, chief medical officer of Medivir, in a press release."We see a continued large engagement in the inclusion of patients in the dose expansion part for the combination fostrox [plus lenvatinib], as an attractive treatment option in second-line treatment. At the same time, there is a clear interest from clinical expertise in fostrox's potential, thanks to the unique and liver-directed mechanism of action, as a combination partner with immunotherapy in earlier treatment lines, which we look forward to exploring further."

In the open-label, multi-center study, investigators are evaluating the combination of fostrox with either lenvatinib, a tyrosine kinase inhibitor, or the anti-PD-1 checkpoint inhibitor pembrolizumab among patients with HCC.² Patients aged 18 years and older for whom current first-line treatment has shown to be ineffective or intolerable are eligible for enrollment in the study. Patients must also 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, and a life expectancy of greater than 12 weeks.

The primary end points include 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.

Previously in February 2023, the company announced that the dose arm with fostrox plus lenvatinib showed to be safe, leading to the commencement of the phase 2a portion of the study. According to these data, the recommended phase 2 dose for the first combination arm of phase 2a is 30 mg for fostrox. This combination also had a good safety and tolerability profile, and no dose-limiting toxicities observed.

Fostrox will be further combined with lenvatinib in phase 2a in patients with HCC for whom first-line treatment has been ineffective or not tolerated. Investigators will assess the safety, tolerability, and to get an indication of the effect of fostrox in combination with pembrolizumab and lenvatinib.

The first 11 patients have already been dosed, and the study is being conducted at 15 clinics across the United Kingdom, Spain, and South Korea.

REFERENCES:

Medivir has completed the dose escalation part (phase 1b) of the 1b/2a study in HCC and focuses on the combination of fostrox and Lenvima. News release. Medivir AB. June 2, 2023. Accessed June 8, 2023. https://tinyurl.com/mc8fdyuj

A study to evaluate MIV-818 in patients with liver cancer manifestations. ClinicalTrials.gov. Updated November 14, 2022. Accessed June 8, 2023. https://clinicaltrials.gov/ct2/show/NCT03781934?term=fostroxacitabine+bralpamide&draw=2&rank=1