The ROCKstar Study of Belumosudil in cGVHD
Corey Cutler explains the ROCKstar clinical trial of belumosudil for steroid-refractory chronic GVHD.
Transcript:
Yi-Bin Chen, MD: And so that's a nice transition to our third agent that's approved for steroid- refractory chronic GVHD, which is belumosudil. And, Corey, you're the lead investigator on these studies. Can you take us through the data here?
Corey S. Cutler, MD, MPH, FRCPC: Sure. So, belumosudil is really the first drug that was developed specifically for the management of chronic graft-versus-host disease. Prior to the study you're seeing here, there was a phase 1 dose escalation trial, and based on that trial, we selected 2 doses of belumosudil to move forward in a randomized design. This was a randomized phase 2 trial. There was no control. And, so, we picked 200 milligrams once daily and 200 milligrams twice daily, and 132 subjects were enrolled. And here, just like in the ruxolitinib trial, the primary endpoint was the overall response rate. But, in comparison to ruxolitinib, it was the overall response at any time, not at a timed response, like…in comparison to the ruxolitinib trial, where patients were allowed to be enrolled with as little as 1 week of corticosteroids. In the past this was really a much more real- world heavily pretreated patient population. They were allowed to have up to 5 lines of therapy, and the median was 4, excuse me, the median was 3, half the patients had more than 4 organs involved. And a huge number of them were really resistant to the prior line of therapy. The graphic here shows the organs that were involved, and you can see it's a fairly typical spread of what we see with the skin, the mouth, the eyes being the most commonly involved organs. And, very importantly, we noted that we enrolled a significant number of patients who had previously experienced ruxolitinib or ibrutinib prior to initiating therapy on this trial. And that's an important thing to note, is that we did enroll patients who were going to be refractory to the other known agents with activity. The response rates are shown here. So overall, the 2 arms behaved equally with an overall response rate of 75%. The CR rate was low, very much like in ruxolitinib. Again, these are patients with advanced sclerosis, advanced ocular disease, where it is effectively impossible to obtain, really, a complete response. What was important, we thought, was that over half of the patients who were treated remained on [the] drug at 12 months. So that tells us the responses are good and the responses are durable. That allowed us to lower corticosteroids and allowed us to lower calcineurin inhibitors as well, including discontinuation in a significant number of patients. And it was on the basis of this trial that the drug was FDA- approved. Also important was that the drug was very well tolerated and safe. There were very few SAEs that led to drug discontinuation, and there were only 3 SAEs that occurred with a frequency greater than 5% at a severity of grade 3 or higher. Again, it's hard to do toxicity in these patients because they're on things like steroids and calcineurin inhibitors, but hypertension, headache, and pneumonia were the 3 most common side effects that occurred greater than 5%, greater than grade 3. So, overall, a very safe and very well tolerated compound.
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