Looking to the outcome of patients with advanced melanoma, at the moment we can say that half of the patients can reach long-term benefit with both immunotherapy and targeted therapy, the other half of the patients, of course, have no benefit from therapy so we need to do more. We need to have a treatment that we can use in first line or in second line after PD-1 failure. So ILLUMINATE301 is an interesting combination with a toll-like receptor 9, IMO-2125, combined with ipilimumab and in phase I it was showing very interesting results from this combination with a good response rate in patients who previously failed PD-1 and also with interesting biomarker data. One of the problems with this local treatment is if we really can get a benefit not only in the injected lesion but also in the distant lesions. This is the background – interesting data from the phase I, now there is the phase III trial in progress, ipilimumab nivolumab plus ipilimumab plus IMO-2125 versus ipilimumab alone. We will see if this is maybe another good opportunity for patients in order to increase the bar of the long-term benefit. ILLUMINATE301 just started, probably we should be able to enrol in 12-16 months all patients and then we need an additional 18 months in order to get the first data.

During this ESMO we also have seen some new data, an update of some previously reported data. So CheckMate-067 is the combination of ipilimumab nivolumab and nivolumab versus ipilimumab. We now have seen the data at four years with a minimum follow up of at least 50 months and it’s interesting to see at four years the percentage of patients still alive with the combination of ipilimumab nivolumab is 53%. You remember that at three years it was 58% so it’s interesting to see that this percentage is still maintained because after three years the curves of the overall survival start to be flat so 53% is consistent with 58% and still with nivolumab now we have 46% that is consistent with the 51% from the three years. So, again, looking to the overall survival there is not a huge difference between these two treatments but still it’s maintained the superiority of the combination, that it’s important still to consider to remember that this trial was not powered to compare ipilimumab nivolumab to nivolumab but there is also other interesting data.

Looking to the patients who are free of treatment after four years and looking at the 53% of patients still after 4 years, 71% of these are treatment free while in the nivolumab it’s just 50%. So with the combination more patients get a benefit, more patients needed not a lot of treatment. Toxicity is still the same so it’s confirmed that it’s toxic but still, so we can get the benefit. Looking to the data in patients with brain metastases reported in July in The New England Journal of Medicine, this is a treatment, the combination, that for sure may be important for the patients with bad clinical characteristics. Another interesting data is looking to the nivolumab data still, anti-PD-1, nivolumab in such cases confirmed to be a very important drug.