Summary of Axatilimab for cGVHD


The clinical trial of a novel agent, axatilimab, is reviewed and analyzed.

Yi-Bin Chen, MD:
But even with ibrutinib or ruxolitinib, and now belumosudil, I think there are many of our patients who cycle through these and do not have what we would judge as optimal responses to therapy. And so there are other agents in development. I think I want to touch on one of them, which is axatilimab. This is a monoclonal antibody that targets the CSF1R receptor that's present, we believe, on activated monocytes and macrophages, which play a role in the process of fibrosis. If we recall about the physiology slide that Corey talked about, fibrosis is that last phase in the pathological hallmark of chronic graft-versus-host disease. It's also responsible for the 2 phenotypes that we've mentioned that are most difficult to treat – the systemic scleroderma patients and the BOS [bronchiolitis obliterans syndrome] patients. And so, this drug is created to target this phenotype. It has gone through a phase 1/2 open-label dose escalation, dose expansion study, as well as a pivotal study that has been accrued. And I do want to review some of that data. I think it's been open at our site, Corey, it's been open at your site as well. So, can you take us through a little bit of this data that was recently published?

Corey S. Cutler, MD, MPH, FRCPC: Sure. So, this is truly hot off the presses and was published in the Journal of Clinical Oncology only weeks ago. This is the early phase 1 or dose escalation trial. And, again, it tells us a couple of things. First of all, the failure-free survival curve on the bottom left or panel D suggests that patients are staying on this compound for long periods of time, which implies both safety and efficacy. We know that this is a real-world patient population, as seen on the bottom right. These are patients with the full spectrum of disease involvement. And similar to the belumosudil trial, they had to have multiple lines of therapy to be eligible for this. The individual patient profiles are on the top right in the swimmer’s plot. But I think what we're all really looking out for is the results of the randomized AGAVE trial [NCT04710576], which we hope to see perhaps at ASH [American Society of Hematology] this year. The AGAVE trial was the phase 2 randomized trial very much like a belumosudil, looking at different doses and dose schedules of axatilimab for patients with steroid-refractory chronic GVHD, most of whom will have been exposed to either ruxolitinib or ibrutinib or belumosudil. So, I think this is the agent to look out for in the future. There certainly are other compounds in development, and other things that we use on a regular basis. But I think this is the next one that will be up for discussion at the FDA.

Yi-Bin Chen, MD: Hopefully, yeah, this was the waterfall plot from the early trial there. And you can see how the majority of patients had somewhat of response from baseline at all different doses, which I think this was quite compelling for all of us to see. And those of us who participated on the study, and the safety. There were a few events, right? This is a monoclonal antibody, that's infusional, and given once every 2 weeks, at least the dose chosen and moved forward and studied in different dosing schemes. There certainly were some infusion reactions, and we did see a certain amount of patients with elevations in their liver function tests or their CPK levels as well. And so those are things we know that we have to monitor for. But certainly, I think all of us did have some patients who benefited from it. And I agree, I think we're all eager to see the results of the AGAVE pivotal study.

Transcript is AI-generated and edited for clarity and readability.

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Yi-Bin Chen, MD, an expert on GVHD
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