IBCD 2016: Integrating assays into clinical trials

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Published: 26 Sep 2016
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Dr Tracy Lively - National Cancer Institute, USA

Dr Lively joins ecancer at IBCD 2016 to discuss presentations from the conference session she chaired.

She discusses the work of Dr Simon Dovedi in developing assays for immune therapy, of Dr Robert Kinders (slides available here) in reproducibility and relevance of assays for clinical trials.

Dr Lively reflects on the debate session from the conference, in which the economics of personalised therapy were considered by representatives of research, regulation and clinical application.

Interviews with other speakers from this session,  Prof Guus van Dongen and Dr Stephen Hewitt, are available through ecancer. 


IBCD 2016 - Innovation and biomarkers in cancer drug development 

IBCD 2016: Integrating assays into clinical trials

Dr Tracy Lively - National Cancer Institute, USA

We had the second session this morning; my co-chair, Dr John Martens from the EORTC, and I co-chaired it and we had four speakers, all of whom we asked to speak to the topic of how to effectively integrate the development of assays for clinical biomarkers into the process of designing and running clinical trials for drug development. So our first speaker is an expert in pharmacodynamic assay measurements, that is trying to determine whether or not a drug that has been given to a human patient has actually engaged its target within the tumour, within the body, and if so has the body with the tumour responded by upregulating something or clinically responding. We are interested in these kinds of assays to figure out if brand new drugs are doing what they’re supposed to do when we provide them to patients and ultimately then if the drug is successful we’d also like to have a successful biomarker that could guide the use of that drug in the patients who would be most likely to benefit from it. Simply discovering the biomarker is just the beginning, there has to be a way to measure it in a clinical laboratory in some type of specimen that you’re able to ask a patient to give you and to have that be measured reliably, robustly and hopefully at a reasonable cost.

Could you tell us a little about Simon Dovedi’s presentation?

Yes, he comes from MedImmune and their focus, or at least the focus of his group there, is developing immunotherapy type agents for the treatment of cancer. That’s very challenging both from the prospect of building the drug itself but also trying to devise some sort of an assay that could predict response because the immune system is so complex and the activity of these drugs, even when they hit their targets, is a little bit more indirect than the sorts of targeted agents that interact with, say, an oncogene product, tyrosine kinase inhibitor, shut down that molecule and then you’ve shut down the pathway that may be driving the tumour. But in the immunotherapy realm you’re trying to activate immune cells which then have to carry out their function of killing the target, killing the tumour.

What did Dr Kinders discuss in his talk?

His job was to provide somewhat of an overview of the things to think about when you’re trying to build an assay, to integrate it into a clinical trial. So how to pay close attention to the quality of the tissue specimen that you have to work with and how to, he likes to say, plan for success. So begin with your end in mind, your desired objective, whether it’s simply to understand how the drug is working or whether you think you might be building an assay for use in guiding therapy further down in the development process. So make sure that you have an assay format, a source of reagents, a stable set-up, so that you can run the assay again if your trial works.

What direction do you see targeted therapy and immunotherapy going in the future?

We’ve had the wonderful experience of seeing some of these drugs work really well. In some cases we’ve had very strong, good clinical responses to treatment if you’ve got the right drug in the right patient. But the challenge is now to figure out how to use the drugs that we have so that we can give it to that patient that is most likely to get one of those really good responses and develop new things for those that we think might need something else. The other question, which is certainly an issue for the targeted drugs, is how to cope with resistance. We’ve certainly seen that problem emerge with some of the first generation of the targeted agents and we trust that there will be similar problems with some of the immunotherapies but maybe not. But certainly with the targeted agents how to keep the response going, what to do if resistance emerges.

What are your thoughts on the debates surrounding personalised medicine and its viability, affordability etc?

We still have so much to learn. At the moment NCI is running a trial that is testing out this model for profiling patients for abnormalities, molecular abnormalities, in their tumours and trying to match them with some novel drug that we hope will be of benefit for them. But it is a clinical trial, it’s a phase II clinical trial where we’re looking for that first signal of efficacy. So it’s not that we can guarantee that if we get a test result we can provide today exactly the right drug, but we’re trying to figure out how to learn how to do that as efficiently as possible.

Do you have any closing thoughts?

I’m just very pleased with the meeting that we’re having where we’re bringing together the oncologists and the folks with the passion for drug development with the laboratory people in actual dialogue so that each understands what the other needs and what the other can contribute to this. Because it is all somewhat new in the drug development area and together with the regulators who, at the end of the day, will need to understand what we’re doing and what works and what doesn’t and enable the final products to get out into clinical practice where the physicians and the patients, in the end, can benefit from it all.