Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results From the KD025-208 and ROCKstar Studies

Belumosudil is an oral selective rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) following an allogeneic hematopoietic cell transplant (alloHCT) in patients aged ≥12 years after failure of ≥2 prior systemic lines of therapy (LOTs). The KD025-208 (NCT02841995) and KD025-213 (ROCKstar; NCT03640481) studies demonstrated that belumosudil was well tolerated, with clinically meaningful responses in patients with cGVHD. KD025-217 (NCT05305989) is a follow-up study that evaluated extended treatment with belumosudil in patients enrolled in the parent studies, KD025-208 and ROCKstar. This pooled analysis reports the long-term follow-up (overall median follow-up duration of 31.4 months) results from these studies in patients with cGVHD. The study included a total of 208 patients across 3 cohorts. Cohort 1 (n=95) received belumosudil 200 mg once daily, cohort 2 (n=92) received belumosudil 200 mg twice daily and cohort 3 (n=21) received belumosudil 400 mg once daily. The primary end point was best overall response rate (ORR). Duration of response (DOR), failure-free survival (FFS) and time to next treatment (TTNT) were also evaluated in this analysis. The best ORR in the modified intent-to-treat (mITT) population was 72%. The median DOR for the responder population was 62.3 weeks (range, 36.1-82.6 weeks). The median FFS in the mITT population was 15.1 months (range, 11.3-20.6 months). The 1- and 2-year FFS rates were 56% and 40%, respectively. The median TTNT was 22.1 months (range, 15.2-40.3 months), where 47% of patients received a new systemic therapy for cGVHD by 36 months. When compared with the published data, the long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained well tolerated with no new safety concerns.