Medivir (MVIR) Status Update summary

Study design and rationale

• Phase 1b/2a evaluated oral fostrox plus lenvatinib in 21 patients with advanced HCC after immunotherapy, in second or third line; safety was the primary endpoint, with efficacy and time-to-event outcomes as key secondary endpoints.

• Patients had Child-Pugh A liver function and ECOG performance status 0–1; treatment was given at 15 sites in the UK, Spain and South Korea, with median follow-up of 10.5 months.

• Fostrox is an oral, liver-targeted DNA replication inhibitor; biopsy findings showed increased DNA damage in proliferative tumor regions and increased hypoxia after treatment.

Efficacy findings

• Investigator-assessed median time to progression was 10.9 months (95% CI 4.1–18.1); ORR was 24%, with median duration of response of 7.0 months.

• More than 75% of patients had target-lesion shrinkage, with benefit reported regardless of response to prior therapy.

• 19% of patients remained on treatment for over a year; the longest-treated patient continued for more than two years with sustained partial response. Three patients remained on treatment at the Aug. 19, 2024 data cut.

• One patient had a partial response followed by progression after 18 months on treatment; liver function and ALBI score remained stable during 1.5 years of treatment.

Safety and tolerability

• No unexpected adverse events or fostrox-related serious adverse events were reported; no fostrox-related deaths occurred.

• Grade ≥3 hematologic adverse events occurred in 11 patients (52%) and were transient, with cyclic neutrophil and platelet recovery before the next cycle; no febrile neutropenia or bleeding due to low platelet count occurred.

• Fostrox dose reductions due to adverse events occurred in 29% of patients and discontinuations in 5%; lenvatinib dose reductions occurred in 57% and discontinuations in 10%.

• Eight possible or related lenvatinib serious adverse events occurred in six patients; one patient discontinued fostrox due to adverse events.