An open‐label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid‐dependent/steroid‐resistant chronic GVHD

Abstract Belumosudil mesylate is a selective Rho‐associated coiled‐coil kinase 2 inhibitor with immunomodulatory and antifibrosis effects. This multicenter, open‐label, single‐arm study evaluated belumosudil 200 mg once daily as second or subsequent line of therapy (LOT) in 21 Japanese patients ≥12 years of age with steroid‐dependent/steroid‐resistant chronic graft‐versus‐host disease (cGVHD). The primary endpoint of best overall response rate (ORR) at 24 weeks after enrollment of the last patient was 85.7% (95% confidence interval [CI]: 63.7–97.0), and the lower limit of the 95% CI exceeded the pre‐defined threshold of 25%. The Kaplan–Meier estimate of duration of response rate at 24 weeks was 75% (95% CI: 46–90); 13/18 responders (72.2%) had a sustained response for ≥20 weeks. The median time to response was 4.1 weeks (range 3.90–8.10); ORR was 47.6% at 4 weeks and 75.0% at 24 weeks; best ORR was 80% for joints/fascia, 66.7% for the mouth, and 54.5% for skin. Overall, 57.1% of patients had clinically meaningful symptom improvement at least once; the median duration of symptom improvement was 22.2 weeks (range 4.0–51.3). Corticosteroid dose reductions were recorded for 57.1% of patients. Median failure‐free and overall survival were not reached. Treatment‐emergent adverse events occurred in 85.7% of patients (most commonly diarrhea, 19.0%), of which 38.1% were drug‐related. There were no drug‐related discontinuations or deaths. In summary, belumosudil 200 mg once daily as second or subsequent LOT in Japanese patients with steroid‐dependent/steroid‐resistant cGVHD was effective, with no new safety concerns.