ASCO 2018 | Master controller drugs: ROR-gamma agonists to boost checkpoint inhibitor response
Ross Camidge, MD, PhD, of the University of Colorado, Denver, CO, discusses single target therapies in thoracic oncology and beyond at the American Society of Oncology (ASCO) 2018 Annual Meeting, held in Chicago, IL. He speaks about ROR-gamma, a ‘master controller’ drug with the potential to revolutionize the treatment landscape.
Transcript (edited for clarity)
One of the things we’ve started to realize is that, although PD-1 and PD-L1 antagonists have transformed the field of thoracic oncology and many other cancers, they really only work in about 20% of people. So the question is, how do you bump that number up? there are a number of other checkpoints: there’s easily 20 different checkpoints. Some have to be on, some have to be off, and people are doing kind of one-on-one experiments: PD-1 plus (mumbles) antagonists; PD-1 plus a CTLA-4 antagonist...
One of the things we’ve started to realize is that, although PD-1 and PD-L1 antagonists have transformed the field of thoracic oncology and many other cancers, they really only work in about 20% of people. So the question is, how do you bump that number up? there are a number of other checkpoints: there’s easily 20 different checkpoints. Some have to be on, some have to be off, and people are doing kind of one-on-one experiments: PD-1 plus (mumbles) antagonists; PD-1 plus a CTLA-4 antagonist. There are some drugs which have the potential to be much more like a master controller, and ROR-gamma is one such master controller. If you use an agonist – so this is an orally available it’s a pill – orally available ROR-gamma agonist, a lot of those other checkpoints that you want to be up go up, a lot of the ones that you want to go down go down. We’ve seen in monotherapy that they are producing responses, so it clearly has some activity, and now there is a trial in progress combining it with, in this case, pembrolizumab, to see if that hypothesis will hold true. Can we, by training a lot of things on and a lot of things off that we hope are in the right directions, can we actually really boost that response rate?
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