Next generation sequencing and WIN therapeutics

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Published: 6 Jul 2012
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Dr Michael Pellini – Foundation Medicine, Cambridge, USA

Dr Michael Pellini talks to ecancer at the 2012 WIN Symposium, Paris, about the investigation of next generation sequencing in the WINTHER project.

 

Dr Pellini and his company are researching targeted therapies and new testing methods, but he notes that these methods are part of a global effort to work through the challenges cancer presents.

 

Dr Pellini sees the WIN Consortium as a group of thought leaders attacking problems from a medical and global perspective. Foundation Medicine’s role in the WINTHER project, short for WIN Therapeutics, is comprehensively profiling each patient’s tumour.

 

Previously, molecular testing occurred with only a few biomarkers analysed. Next generation sequencing gives a much larger picture, but is very complex and expensive. Another aim of the study is to make this method practical and accessible in all clinical settings.

 

Filming supported by Amgen

WIN 2012, June 28-29, Paris, France

 

Next generation sequencing and WIN therapeutics

 

Dr Michael Pellini – Foundation Medicine, Cambridge USA

 

 

We’re here in WIN 2012 in Paris and Dr Mike Pellini, you are here with us, you are the CEO of Foundation Medicine. Can you talk about your involvement with WIN?

 

We got involved in WIN about a year ago. We knew some of the founders of the consortium, Dr John Mendelsohn from MD Anderson, certainly, has just been a thought leader in the space for many, many years. One of the great challenges in the world of oncology going forward is that we’re dealing with an enormous amount of new information that’s emerging. We have many molecular tests that are being ordered, we have many targeted therapies that could potentially attack those targets that the tests are searching for but there aren’t enough efforts globally that are really trying to work through all the challenges in the space. So with the WIN consortium we saw just a group of thought leaders that were not only attacking the problem from a science and medical standpoint but they were thinking about just going… they were attacking it from a global perspective. So it was not only unique in terms of the trial itself and just thinking about the amount of molecular information that is emerging, but it was unique in the perspective that they’re really looking at this cross-continent and there’s no other group in the world that I know of that is really thinking that way today.

 

So two words about the trial, it’s called the WINTHER trial for WIN therapy, if I’m not mistaken, and it’s an FP7, a European granted, it got three million, I think, and it got incredibly high votes?

 

Correct, it did extremely well in the prize, it has done extremely well in the process so far.

 

And you are going to be doing all of the next generation sequencing for this trial.

 

We’ll be doing the comprehensive profiling of each tumour. So what that means is, historically to this point in time, the way that molecular testing has occurred in cancer is that a sample is received and somebody would have to select three, four or five biomarkers that one would want to test for. What we’ve recognised, not we as a company but we just as an oncology community, what we’ve recognised over the course of the past couple of years is that we are missing far too much with regards to the tumour if we continue to think about things on a one-off basis: this is a test I want to order, this is a test, this is another test. What we’ve learned is that it’s very difficult for even the best and brightest oncologists in the world to outsmart the tumour. It can’t be done, we get surprised every single day with the findings that emerge as we really interrogate the tumour with our molecular testing approach. So in essence what we’ve said is let’s reshape the way that we think about the problem of uncovering the molecular drivers to each patient’s cancer. Let’s use the technology which is finally ready for the clinic, because even a couple of years ago it wasn’t, and let’s let the cancer tell us what the key features that are driving this cancer forward are. So then the clinicians and the pharmaceutical companies can start to attack those critical molecular drivers on a very specific basis. So it’s really an entirely different way of thinking about how one can interrogate what is driving each individual’s cancer.

 

And how do you go about doing this?

 

We use a technology called next generation sequencing, as you’ve mentioned. It is a complex process, there is a reason why it’s not deployed all over the world right now. It’s one thing to utilise the technology, for example, in a blood sample, blood is very homogenous but tumour tissue is very heterogeneous and in order to use this technology first of all in such a complex disease, one of the things we’ve heard in many presentations today is just the sheer complexity of cancer, we understand that but that means there’s complexity of the tumour tissue itself. We’ve also brought this technology forward to be used not on research grade samples but we want this technology to be utilised on just the routine clinical grade samples that are collected by surgeons, by oncologists, throughout the world. If we bring a technology to the market and it can only be used in a small subset of patients, what’s the point of bringing it to market for the most part? There are times when that can still be useful, however, taking this technology and applying it to just the routine clinical specimens that are used in clinical practice today, to be able to scale this technology so you don’t just run it on a one-off basis but you actually have a process where you can run tens and ultimately hundreds of samples per day. And then not only generating the data is challenging but there’s an enormous amount of data that comes from each patient’s sample and so you have to look at it and say, OK, what’s relevant for clinical practice, what isn’t relevant? What we then do is only report out the information that’s clinically relevant, we do that via the internet, we do that on medical reports that we issue. And so there really is a complex process that we go through from the time that we receive the sample, through the sequencing, all the way to the back end when we report this information out to the oncologists so that they get it and they understand what to do with it. This whole process is wasted if an oncologist looks at the information and says, “What is this? What do I do with this?” So what we have to do, as a company and just as an industry now, we have to present data in a way where the oncologist, when he or she picks up that report or looks at the information on the internet, first of all they say, “Right, I understand this. I understand what this information is, at least the way it’s presented makes sense,” number one, and number two, “It’s helpful to me as I think about the way that I am going to treat my patients.” If we accomplish those two things, we play a key role in really changing the practice of oncology. Really, we’re on the threshold of doing that right now and the oncology world is undergoing really dramatic changes.

 

And Foundation Medicine, it’s not a huge company is it?

 

No, we’re not a huge company, we are a young company and so similar to the WIN consortium. We’ve been around about two years, we’re based in Cambridge, Massachusetts. Some of the founders of our company are really the world leaders in terms of understanding cancer biology and genome technology and it’s really a convergence of understanding the science, understanding the medicine and understanding the technology, not to mention all the information technology that goes into this that really allowed foundation medicine to come into being. Our sense is that we are a couple of years ahead of anyone else in the world right now in terms of being able to utilise this technology just for routine clinical use. Then we’re constantly pushing in terms of where the technology can be used next. Right now there’s a focus on DNA, we’ll then go to RNA and think about combining those two pieces. We still have a lot to learn about how to best use this technology in the clinic for the long term but right now we’re generating information and providing it to pharmaceutical companies and oncologists in a way that’s never been done before and the early results have been extremely positive.

 

So it’s a two year study, it’s a proof of concept study, if I understand correctly?

 

The WIN study?

 

Yes.

 

The WIN study is a two year study as it stands right now and, again, one of the most exciting things about it is not only the fact that it’s actually looking at really trying to match specific therapy to each individual patient, not groups of patients but it’s literally one therapy to one patient, perhaps two or three therapies to one patient. That’s unique. The second aspect that’s so unique is the fact that, again, this is a global trial. I’m hard pressed to think about another global trial that’s not simply being run just by a pharmaceutical company. So the notion or the recognition that cancer is a global disease and we need to think about it as such, maybe not only think about it as such but act in that manner, is something that I think is extremely important that WIN has done.

 

Yes, well let’s hope this pilot target study after two years will lead to a much bigger study.

 

I couldn’t agree with you more.

 

Thank you. Thanks for taking the time.