WINTHER: The WIN therapeutics clinical trial

Professor Josep Tabernero- Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

What is the WIN consortium and what is the organisation trying to achieve?

WIN is an innovative and integrative concept of academia as well as pharma companies, small biotechs and also diagnostic companies in order to move forward in the way that we develop new drugs in patients with metastatic cancer. So basically the concept here is that you can integrate in one unique platform, in one single platform, different companies at the same time, even different pharma companies and different diagnostic companies, in order to personalise more and more the treatments that the patients receive. This is really very unique and very innovative and you may realise that putting altogether a set of ten different pharma companies as well as a minimum of five diagnostic companies, small biotechs, bioinformatics resources, to build one unique project to demonstrate that personalising the diagnostic and personalising the treatment based on the molecular profile of the patient, of the tumour of the patient actually, is going to benefit in terms of survival. This is the unique approach. It may seem that a project that is running for more than four years, actually four years now, has not evolved a lot but actually this is not the case.

We have the first clinical trial on-going, the so-called WINTHER, in four different institutions worldwide. This means the Institut Gustave Roussy in Paris; this means also Vall d’Hebron University Hospital in Barcelona; the MD Anderson in the United States and other centres in Israel. To make this simple, actually, means that you have to take into consideration personalising the diagnostic with molecular profiling indicating different drugs from different companies and therefore different regulatory alternatives because even France and Spain are in the European Union and the time of the regulatory authority’s approval for a specific trial, these are completely different drugs. And, as mentioned before, it’s really a success that we have arrived here and we have been able to start this trial. This is the first one, there are also two other trials that have been considered this year and these are more diagnostic trials concerning or referring to circulating free DNA as well as validation of different diagnostic tests within the centres. But definitely the platform is moving forward.

Also the opportunity that you had at the WIN meeting in Paris is to make real-time interaction with different pharma companies in the same room and discussing the pros and the cons of this approach as well as the diagnostic companies. So it’s an integration of several different aspects that are critical in order to develop drugs in a more efficient way.

Can you tell us more about the WINTHER clinical trial?

The WINTHER trial is a fascinating trial that it’s developing patients with all tumour types, all comers. So at the time that these patients are refractory to conventional treatments, they are going to get a tumour biopsy in real time and also a biopsy of the normal tissue where the tumour was generated in order to be able to compare the data, genomic and proteomic profile and RNA profile, in both the normal tissue and the tumoural tissue.

With this data, with this profiling, if we find any driver mutation or alteration for the tumour the patient will be treated with the drugs that are available for this oncogenic phenomenon. But on the other hand, if we don’t find any oncogenic driver we will do molecular profiling for this patient and actually with the data that is generated with the compilation of all the proteomic and genomic profiling we will establish some signatures and, according to these signatures, this patient is going to be treated with the preferred treatment option according to the pathways that are up-regulated or deregulated in this tumour. So it’s like a two armed study whether the patient has an oncogenic phenomenon, the patient is going to be treated according to this, and if the patient does not have this oncogenic property he’s going to be treated according to the results of the molecular profiling.

At the end what we want to see in the two arms of the study is that patients receiving a tailored treatment according to this data actually have a higher progression free survival than the progression free survival that they had in the previous treatment that they received. So we are going to compare in each patient, each patient is going to be the internal control for the benefit of this treatment compared to the previous treatment.

So we have raised a hypothesis that we want to have a ratio of the progression free survival in the new treatment compared to the previous one of more than 1.5, 40-50% of the patients included in the study.

Has accrual into WINTHER already started?

The study at this time point has been completely approved by all the institutions and now we are in the process of starting the trials. So the hope, again, in this study is that by December 1st we are able to recruit patients in the four institutions.

Why include all-comers and not target one tumour type?

The important concept of the WINTHER trial is that it’s not focussed on tumour types, it’s focussed on deregulations and on gene alterations so that’s why we love all comers. So all comers are going to be analysed, the tumours are going to be analysed, the normal tissues are going to be analysed and we are going to see innate signatures, signatures that may be related to an oncogenic event or to an non-oncogenic event, but the concept is that we are going to treat patients according to the signatures not to the tumour type. That’s why all comers can and actually have to enter in the trial.

Are there any particular data or topics presented at the WIN symposium that you would like to mention?

The most important concept of WIN is that this approach is feasible, reliable, this is going forward so all companies can be integrated – pharma companies, diagnostic companies. Naturally, one important thing that we do in the WIN Symposium on an every year basis is to put all the information that all the parties have available to the whole group. So, for example, it’s a matter of, for example, we presented this year how the profiling of the PI3K pathway that we did in our institution in patients that were entered in clinical trials of patients targeting the PI3K pathway, how was it implemented, and actually which were the results of doing this molecular profiling in patients with these characteristics. We did this approach with PI3K inhibitors, others did it with RAF inhibitors and RAS inhibitors. So the message here is that within the WIN symposium we are able to put all this data in together.

How far away are we from getting personalised medicine truly integrated into routine clinical practice?

The WIN platform and the WINTHER trial, it’s a hypothesis generating study so this approach moves in the right direction or has a trend in the right direction. The next step is going to be that we should convince the authorities to think on the way that they discuss and they evaluate clinical trials. My perception and the perception of most of the WIN components is that we cannot continue developing new drugs in the way that we have been doing so far, this means including thousands of patients in phase III clinical trials that are really very expensive and at the end the benefit is quite marginal for most of the patients.

What is your home message on the WIN Consortium?

WIN is the fastest way to make real personalised medicine in the cancer field.