AACR 2025 | Assessing the interchangeability & dosage of checkpoint inhibitors

I’m giving this talk at AACR, looking at if we can reduce the dosages of some of the checkpoint inhibitors, as well as if they’re interchangeable. So there’s been a lot of work in the past few years, looking at the dosages of checkpoint inhibitors. We’ll just start off by discussing the fact that these checkpoint inhibitors are phenomenal new advances for patients. For some patients, melanoma has really transformed survival outcomes for these patients. But unfortunately, many patients lack access to these therapies because of financial concerns, or they’re able to receive the therapies but incur considerable financial toxicity. So one of the solutions and approaches that’s been developed to look at this is if we can give a lower dose and actually maintain the same level of efficacy. And there’s substantial data to show now that the fact that the FDA-approved dosages are far higher than is actually necessary in order to achieve the outcomes that we want. And so, for example, you know, pembrolizumab is dosed at 200 milligrams per kilogram, but we know from all of the pharmacokinetic data, such as 2 milligrams per kilogram every three weeks will bring exactly the same outcome. We’ve seen this from numerous studies. And then the question is, can we go even lower? That’s a 90% dose reduction, but can we go even lower? And if we look at nivolumab, the dose receptor occupancy was the same in the phase one studies when you’re using 0.3 milligrams per kilogram. And also there was a Phase II randomized trial published in 2015 at all different dose levels showing no dose response relationship and that very low doses should have significant efficacy. And so it’s suggested that we can also use, you know, very low doses, even 5% to 10% of the actual FDA-approved dose and get the same clinical outcomes. So really, that’s what I would say there regarding that, that there’s really great opportunity to reduce the dosages in order to expand access. And then with regard to interchangeability, one of the concerns is that the cost is very high, but if there’s real competition within the marketplace, then the purchaser can do negotiations with the manufacturers and see who gives the lowest price. And so we’ve got different indications for these checkpoint inhibitors, lung cancer, melanoma, kidney cancer, all different, and trials designed in many different ways, some with biomarkers of PD-L1, some without, some with chemo, without chemo, et cetera, et cetera. But if you actually compare some of the similarly designed trials and try to compare apples to apples, you can see that mostly the responses or the overall survival is relatively similar between many of these agents. And, you know, we’ve collated a lot of this data with overall survival forest plots between trials. And that’s in a paper that we published in BMJ Oncology a few years ago. And so we’ll be discussing those data.

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