SPRING – rolling tri-therapy combinations of targeted drugs in second line of metastatic NSCLC

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Published: 3 Jul 2015
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Prof Razelle Kurzrock - University of California, San Diego, USA

Dr Kurzrock talks to ecancertv at WIN 2015 about the SPRING trial, one of the next set of trials being planned by the WIN Consortium following on from the seminal WINTHER study.

In this SPRING trial, advanced genomic profiling will be used to help guide second-line therapy for patients with metastatic nonsmall-cell lung cancer which will consist of a combination of three of the most appropriately targeted drugs.

SPRING – rolling tri-therapy combinations of targeted drugs in second line of metastatic NSCLC

Prof Razelle Kurzrock - University of California, San Diego, USA


SPRING is the next generation trial; we started with WINTHER and now we’re going to SPRING, I guess this is the seasons. But it’s the new trial that we’re planning and we’re planning it for lung cancer patients. Obviously patients with metastatic lung cancer do very poorly and we really want to improve how they do and we’re looking for longer survival periods. What we’re doing for SPRING is we’re using cutting edge genomics and transcriptomics, which is RNA analysis, and we’re integrating both of them and we’re not going to treat with just one drug that is matched but with a combination of three drugs. So those are the two essential features, going from single therapy to customised combination therapy and using really advanced genomics and transcriptomics to profile patients.

What is the proposed study design and methodology?

Patients that have lung cancer and have been treated on one or two standard therapies and are not doing well generally will live about 6-10 months. So obviously we really want to do something that’s transformative. Those patients will get a biopsy of their lung, the normal lung tissue and the tumour, and that will be compared. Then we’ll do this advanced molecular profiling, we will subject that to an algorithm that we call SIMS that will help us decide what is the best therapy. The intention is to give three drugs that are customised to that patient’s molecular portrait.

Why the decision to use three drugs in combination rather than try two first?

There’s already a lot of experience with one drug and we know that one drug that is matched to patients can work. Patients get better but they rarely go into complete remission and the remissions that they do go into don’t last long. The patient may get better for three months or six months but inevitably that’s it, then they relapse. We understand why – by the time you have advanced cancer there are many things that are wrong in the tumour. So we believe if we went to two drugs we might do a little bit better, but if we go to three drugs we really think, based on the science, that we can hit many of the pathways.

How will investigators decide on which three drugs to use in combination?

We will do the biopsy and then we will run what we call genomics, which analyses the DNA, then we will run the RNA analysis. Those two analyses will be integrated through our bioinformatics system and we have an algorithm for analysis of very complex data that will be simplified. It’s called SIMS, the S in SIMS is for simplified, so it simplifies very complex data and tells us what are the optimal three drugs for that particular patient.

Which countries will participate in the trial and what about access and availability to the most appropriate drugs?

That’s a very important question. We plan to make it an international trial. The WINTHER trial was conducted in France, Spain, Canada, Israel and planned in the United States as well and we believe that the same countries should be involved in SPRING but after the initial stages where we get used to the new trial we would really like to expand it to our partners, really throughout the world.

What is it hoped that the SPRING trial will achieve?

We want to be careful that we don’t over-promise so we have what we want to do is perhaps double the amount of time that the patient spends in remission and really look at five year survivals and have a real impact on five year survival.

When is the SPRING trial likely to start?

The protocol, a preliminary protocol, is written and we brought it to the Symposium here where we had many experts that we could get input from. We got a lot of good information from them so we plan to do the next round of the protocol design over the next month. I would like to think that the protocol will start in the first quarter of 2016.