The ROCK2 inhibitor belumosudil produced high response rates and improved quality of life in patients with chronic graft-vs-host-disease (cGVHD), according to results from a phase 2a trial published in the Journal of Clinical Oncology.

“Data from this study are very encouraging, given the unmet needs of patients with cGVHD,” the study authors wrote.

The authors explained that ROCK2 is activated in the T helper 17 (Th17) cell-skewed milieu of cGVHD, which results in the activation of STAT3 and promotes expression of Th17-specific transcription factors.

Continue Reading

Selectively inhibiting ROCK2 is known to restore immune homeostasis, so the authors wanted to determine if ROCK2 inhibition with belumosudil is safe and effective for the treatment of cGVHD.

The phase 2a trial of belumosudil ( Identifier: NCT02841995) included 54 patients who developed cGVHD. The patients had undergone allogeneic hematopoietic stem cell transplant to treat acute leukemia, myelodysplastic syndrome, or non-Hodgkin lymphoma.

At baseline, the patients’ median age was 52 years, and 63% of patients were men. Roughly half of patients had received myoablative conditioning (44%), and most (89%) received peripheral blood stem cells. Donors and recipients were fully matched in 83% of cases.

The median time from diagnosis of cGVHD to study enrollment was 20 months. Most patients (78%) had severe cGVHD, 20% had moderate disease, and 2% had mild cGVHD. The median number of prior therapies for cGVHD was 3, and 73% of patients were refractory to their last treatment.

In this study, patients received 3 different doses of belumosudil: 200 mg once daily (cohort 1), 200 mg twice daily (cohort 2), and 400 mg once daily (cohort 3).

In the entire population, the overall response rate (ORR) was 65%. The ORR was similar across the cohorts — 65% in cohort 1, 69% in cohort 2, and 62% in cohort 3. The ORR in patients with severe cGVHD was 66%.

Most responses occurred within 8 weeks of starting belumosudil. The median duration of response was 35 weeks, and the median time to next treatment was 14 months. The overall survival rate was 91% at 12 months and 82% at 24 months.

During belumosudil treatment, 50% of patients had a clinically meaningful improvement in quality of life from baseline.

Belumosudil was considered well tolerated, with 9% of patients requiring dose reductions and 3 patients discontinuing belumosudil due to treatment-related adverse events.

Treatment-related adverse events occurred in 56% of patients, but none of the events were considered serious.

“Belumosudil was well tolerated and achieved clinically meaningful responses in patients with cGVHD across all dose regimens evaluated,” the study authors concluded.

Disclosures: This research was supported by Kadmon Corporation, LLC. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Jagasia M, Lazaryan A, Bachier CR, et al. ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease. J Clin Oncol. Published online April 20, 2021. doi:10.1200/JCO.20.02754