I presented today the results of the phase III trial, the METIV-HCC phase III trial of second line tivantinib versus placebo in MET high advanced HCC. The background of the study is that we ran a phase II study which demonstrated that tivantinib worked in patients with high MET expression subtype of hepatocellular carcinoma. So based on the results of the phase II study we ran the phase III enrolling only patients with MET high HCC. It was a randomised phase III study, tivantinib versus placebo. We enrolled 340 patients, 226 received tivantinib and 114 received placebo in second line after standard treatment, that is sorafenib. All these patients had high MET expression. Tivantinib is a MET inhibitor so the primary aim of the study was the overall survival of these patients treated with tivantinib.

The baseline characteristics of the patients were well balanced in the two study arms and were quite similar, as in other HCC studies. We evaluated patients with high MET expression both pre-treatment with the sorafenib and after treatment with sorafenib. The survival of these two groups was the same.

Unfortunately the study is negative, we didn’t see any advantage in terms of survival with tivantinib compared to placebo. We deeply analysed our data to find an explanation for this negative data compared to the phase II that was positive and we found some differences between the phase II and the phase III study. But the most relevant point is that the overall survival of patients on placebo is quite long, nine months, that is longer than any prior reported survival in HCC. So probably we selected a more favourable population compared with the population we selected in the phase II. So we couldn’t find any difference between the placebo and the tivantinib.

With regards to the toxicity of the drug we confirmed the toxicity profile observed in the phase II. We observed some grade 5, so death, of patients on tivantinib but only three events, that is 1.3% that are considered related to the study drug. So the drug is not toxic. But, as I said, unfortunately the study is negative so tivantinib doesn’t work in this population.

Are there any plans to try and find a way in which tivantinib might work for someone?

I’m not aware of any plans of the sponsor to keep on developing tivantinib. We are trying to analyse more deeply our data to find more explanation or clarification of these results and then we will write the paper with a complete set of data.