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Checkpoint Inhibitors in Combination With Novel Therapies for Recurrent GBM
Dr. Shah: So, we’re here at the Society for Neuro-Oncology annual meeting and you are presenting a very interesting study on two novel agents in combination with checkpoint inhibitors. Could you tell us a little bit more about these agents and why you feel they have promise?
Dr. Lim: Sure. So, I think that there’s been, with all this great excitement for all these immunotherapy agents, glioblastoma hasn’t been as responsive to immunotherapy as other tumors, so this is, you know…this project is part of a concerted effort to try to understand glioblastomas at a deeper level. And so what we’ve done is we’ve studied glioblastoma specimens from patients and we’ve come to realize that there are other mechanisms of immune evasion and certain molecules such as anti-LAG3 seem to be upregulated in patients with glioblastoma in addition to PD-L1. So we thought a natural next step in these combination therapies is to look at these agents such as anti-LAG3 and anti-CD137 in combination with PD-1 and alone and try to understand if we can do better. And what’s really exciting about the anti-CD137 is that it’s what we call an agonist. It’s something that doesn’t prevent T cells from turning off but actually turns T cells on.
Dr. Shah: Okay. So in that sense, it is potentially synergistic with the PD-L1 or the innovation of the checkpoint blockade?
Dr. Lim: So yes, absolutely, we think that there could be a potential synergy. And we’ve actually done preclinical studies and shown that it works both the LAG3 and the CD137 work very well or are synergistic with anti-PD-1.
Dr. Shah: And could you tell us a little bit more about the study that you presented over here? How was it designed? How many patients and what kind of data did you get?
Dr. Lim: Sure. So we’re actually still in the midst of the study and it’s a phase I, multi-arm study. It’s an open-label study where we’re basically trying to find a maximal tolerated dose. And then once we find the maximum tolerated dose, we’re doing a dose expansion. And so, you know, we’re at the top levels of anti-LAG3 alone and at the highest levels of anti-LAG3 and PD-1 as well as with the anti-CD137 alone and anti-CD137 with PD-1. And right now, we’re able to show very nicely that it’s safe either in combination or alone, and you know, I’m optimistic and we’ll hopefully have some survival data to present to you by, you know, middle of next year.
Dr. Shah: Actually, that leads me to one of the questions I had that if these agents are synergistic with checkpoint inhibition, then I was worried that you might see greater toxicities, but it seems that you are not seeing that signal so far.
Dr. Lim: Right. So we haven’t. I mean, we’ve also had the benefit of being able to look to some of the other tumors that have tested these agents and so we’ve been able to have some guidance with the doses that we’ve chosen.Additional Info
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