WIN Symposium 2015 highlights

Prof Richard Schilsky - Chief Medical Officer of the American Society of Oncology (ASCO)

This has been an exciting meeting. I think for me, so far, the two main highlights really were the lectures by Andrea Califano and Jim Allison. Although they were quite different, I think they illustrate a very important principle. Dr Califano’s lecture highlighted the enormous complexity of cancer and the fact that it may be possible, through very careful and innovative analysis of molecular networks, to identify key nodal points where there are master regulators of those regulatory pathways that, if targeted, could potentially have a major impact on the treatment of cancer. But what he really illustrated was just how complicated each cancer can be. Now, Dr Allison had the perfect response to that which is that the only thing more complicated than cancer is the immune system and the ability of cancer to generate heterogeneous sub-clones can easily be matched by the ability of the immune system to generate enormously heterogeneous responses. So we’re beginning to see now the enormous promise of immune therapy in treating cancer and the fact that it seems to be able to be effective against essentially every kind of cancer because it’s agnostic with respect to things like histological type or mutational status. So these two concepts about the heterogeneity of cancer and how to understand it and target it and the capacity of the immune system to match that heterogeneity and then kill the cancer in a tissue agnostic way are really two of the real highlights of the meeting.

Considering the complexity and variability of the immune response, could you comment on the presentation by Dr Angel Porgador and how the immune response can be measured?

One of the keys there that his lecture and others, other researchers are working on, are signatures of immune response that can predict which cancers are more or less likely to be susceptible to attack by the immune system and by which components of the immune system. Because of the great expense associated with modern cancer therapies it’s becoming more important than ever before to be able to identify the patients most likely to benefit from any particular kind of treatment. Because to say that we can afford to just treat everybody is unrealistic, no healthcare system is going to be able to sustain that. So we have to really be able to understand the biology well enough to develop the biomarkers to understand which patients require which therapies and then focus those therapies on those people in particular.

Can you give an overview of some of the main points made during the plenary session on the next generation of trials with targeted therapies?

We talked in that session, in the round-table, primarily about strategies to overcome drug resistance. I don’t know that we drew any major conclusions from that except to say that combining drugs is complicated, not only in terms of selecting which drugs to combine but how to combine them, how to derive the doses of the drugs that can be given safely in combination, how to sequence the drugs – is it necessary to give three drugs together, can you give them sequentially in some way, how to determine a biomarker for the impact of a drug combination on a patient’s tumour. So all of these were points that came out during that discussion. We talked a little bit about also combining small molecules with immunotherapy because I think people all see some value in doing that. Again it’s a question of how to do it, how to do it safely. So that was really the focus of that conversation. Then in the second part of that session we really began to get into a review of the WIN portfolio of clinical trials so we had an update on the status of the WINTHER trial and that, of course, was the first of the WIN trials. One of the novel things about WIN is that it’s, in a sense, been willing to go where no other trial or organisation has been willing to go which is to go immediately to combination therapies in very difficult to treat cancer and to approach it in a very innovative way and to engage a representative group of institutions from around the globe to tackle the problem.

Following on from WINTHER, what are some of the other trials being conducted by WIN?

Well, there are none being conducted yet but there are three being planned, all in lung cancer. One is a tissue acquisition platform study called BOOSTER which is a study designed to identify biomarkers of people who are likely to have or develop lung cancer. So that’s a study in which patients who are newly diagnosed with lung cancer will have pre-treatment biospecimens obtained, both blood and serum and tissue, all the biomarkers are yet to be decided. Then we’ll have definitive surgical resection of their cancer, the tumour will be obtained and normal lung tissue will be obtained and then we’ll have in the post-operative period sequential acquisition of additional biospecimens. With that and, of course, we capture the long-term clinical outcomes from these patients, so with that we’ll have a very rich dataset of biomarkers and clinical outcomes that can be used to identify those biomarkers that might actually be useful in either identifying a cancer very early on or monitoring for recurrence.

Then you’ve got the SUMMER trial which is really an adjuvant post-operative therapy trial for patients who have a resectable lung cancer and for whom adjuvant post-operative treatment is a standard of care. The idea of SUMMER is to randomise patients between a standard of care treatment, presumably chemotherapy, versus chemotherapy with one or more targeted agents with the targeted agents to be selected based upon the SIMS algorithm for identifying targeted treatments.

Then the third trial, the SPRING trial, is for patients with metastatic non-small cell lung cancer. That trial has been the most controversial so far with respect to its design but the ultimate goal of SPRING is to improve the five year survival rates for patients with non-small cell lung cancer by giving three targeted drugs in combination. The hard part is to figure out which three drugs to use because the three drugs might be different for different patients because of this whole issue of cancer heterogeneity. That’s where things like the SIMS algorithm which allows one to interrogate a cancer both with respect to its mutational profile and its transcriptional profile and then integrate that information using the algorithm to identify the drugs most likely to be effective, that’s what needs to be tested out in the SPRING trial.

What are some of the regulatory and funding challenges facing clinical trials in personalised cancer medicine?

I think the challenges are several fold. So every country in the world has a regulatory authority, a health authority, that regulates whether new products can enter the medical marketplace. The new products can take the form of drugs or they can take the form of devices or tests or other types of medical products that are used either as machines or prostheses or whatever. The regulations that apply to authorising drugs for marketing are different from the regulations that apply for tests, that apply to tests entering into the marketplace, and of course different jurisdictions over the world have different laws and different regulations. So if you’re trying to do global clinical trials like we’re trying to do in WIN where you have countries all over the world participating, obviously the ability of each country to launch a trial depends upon its regulatory authorities and it has to be able to comply with its local laws and regulations. So, to the extent that these can be harmonised to the greatest extent possible, it would greatly facilitate the launch of global clinical trials, otherwise you find that one country can launch, another country can’t launch until two years later. So the goal of the round-table is to have a conversation between the academic clinical trials and the regulatory authorities about what are the challenges, what are the goals, what are the obstacles to achieving some degree of harmonisation on regulatory principles that will allow these global trials to launch in a much more comprehensive way across multiple countries, multiple jurisdictions, all at the same time.

Do you have other comments to make about the WIN Symposium 2015 scientific programme?

The WIN Symposium programme this year has been fabulous, it’s been forward looking, it’s been creative; we’ve had wonderful speakers. The Symposium, in a sense, is the most visual part of WIN but a lot of the most exciting parts of WIN come from the engagement of all the WIN participating institutions and the development of what I think are a very innovative suite of clinical trials.