The background of this study is about testing a new drug which is an IAP inhibitor, xevinapant, in locally advanced squamous cell cancer of the head and neck. This study was already presented two years ago showing early promising results and at the moment we are having an update of the study with long-term follow-up. This is what was presented at ESMO.
This study was a phase II randomised trial, placebo-controlled, in patients with locally advanced squamous cell cancer but these patients were high risk patients, essentially stage 4 and HPV negative, heavy smokers. So the most advanced locally advanced cases. The patients were randomised to xevinapant plus cisplatin radiotherapy, which is the standard of care, versus the same standard of care plus placebo.
As I said at the beginning, the study was already presented. We knew that the primary endpoint was met, the primary endpoint was local regional control at 18 months, significantly improved with xevinapant compared to placebo. We knew also before this update that progression free survival was markedly improved with xevinapant compared to placebo at three years. Now we have an update which is showing long-term follow-up and at five years there is a significant improvement on overall survival, which is new, and it’s an important improvement because we have nearly a doubling of overall survival at five years for xevinapant compared to placebo.
These findings could be really important because this is the first time in decades that we have superiority in overall survival when compared to the standard of care, cisplatin radiotherapy. It never happened before so we have to consider these results as really promising. But the problem is that the study was not powered for really changing the practice because there are only 96 patients who were randomised and we need a confirmatory study with more patients on the same selection of patients.
So this is what is happening at the moment. We have a confirmatory phase III large-scale randomised trial which is the TrilynX study. We are now waiting for the results of this phase III trial. If we have a confirmation it will be definitely changing practice for this type of cancer.
We have also to emphasise that this drug is active, that’s what we see in the outcome of the study, but also the drug, when combined with cisplatin and radiotherapy, is well-tolerated because we don’t have really an increase of toxicity; especially when we look on the long-term toxicity there is no difference between the two arms, suggesting that there is a benefit on efficacy without increasing the toxicity.