Medivir (MVIR) Study Update summary

Treatment rationale

• Fostrox is an oral prodrug of troxacitabine, designed for >100-fold liver-targeted exposure vs traditional IV chemotherapy; its cytotoxic L-nucleoside approach aims to spare normal cells and avoid resistance.

• Rapid liver conversion generates the active metabolite; DNA damage may increase tumor antigen presentation, while TKI-induced hypoxia may increase active metabolite levels.

• Traditional IV chemotherapy has not been used in HCC because doses needed for liver exposure can be poorly tolerated amid cirrhosis, liver toxicity sensitivity and local drug inactivation.

• Fostrox adds a DNA-damage mechanism to systemic approaches based on multikinase inhibitors and checkpoint combinations, with potential for combination treatment.

Clinical development and phase Ib findings

• Fostrox plus lenvatinib RP2D was 30 mg; the phase Ib/IIa combination study was fully recruited and ongoing at 15 sites in the UK, Spain and Korea.

• All six phase Ib patients had progressed on prior treatment; 83% had received atezolizumab plus bevacizumab in 1L and 50% had prior TACE.

• Independent RECIST 1.1 review found stable disease in 5 of 6 patients; mRECIST review found 3 responders, including 1 complete response.

• Grade ≥3 adverse events occurred in 50%; transient neutropenia was most common, with no febrile neutropenia. Lenvatinib and fostrox dose reductions occurred in 50% and 17%, respectively.

HCC treatment context

• HCC has substantial unmet need: 80% of patients are diagnosed at an advanced stage, with 5-year survival below 20%; cirrhosis also limits treatment tolerance.

• Advanced HCC treatment has evolved toward immunotherapy and TKIs, while chemotherapy combinations remain largely unexplored; systemic treatment is also being considered at earlier disease stages.

• The treatment paradigm shifted from sorafenib and lenvatinib monotherapy in 2007–2018 toward combination regimens from 2020.