About the ROCKstar Study
Trial Name: Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy
ClinicalTrials.gov ID: NCT03640481
Sponsor: Kadmon, a Sanofi Company
Completion Date (Actual): December 2023
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Study: Belumosudil Decreased Collagen, IL-17 Levels for Skin, Oral cGVHD
The study is a companion study to the ROCKstar study, which investigated the drug in individuals with cGVHD who received 2 to 5 prior lines of therapy.
Following 6 months of treatment with belumosudil (Rezurock; Kadmon Pharmaceuticals), individuals with skin and oral chronic graft-versus-host disease (cGVHD) had a significant dose-dependent tissue-specific decrease in collagen levels, according to an abstract presented at the 2024 Tandem Meeting for Transplantation and Cellular Therapy Meetings of American Society for Transplantation and Cellular Therapy and Center for International Blood and Marrow Transplant Research.1
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Furthermore, investigators also found a reduction in interleukin (IL)-17 and transforming growth factor (TGF)-β cytokine levels, which they said suggested a rho-associated coiled-coil kinase 2 (ROCK2) “inhibition-induced reduction in tissue fibrosis, as marked by collagen content, and inflammation,” according to the abstract.1
Belumosudil is an oral ROCK2 inhibitor that has been approved by the FDA in the third line for cGVHD and has been demonstrated to reduce peripheral blood IL-17 activity and regulatory T-cell recovery post-inhibition. However, investigators previous studies did not aim to determine the response directly in affected tissues. Therefore, this study included results on tissue-level cGVHD after 6 months of treatment with belumosudil for oral mucosa, salivary glands, and skin.1
The study was a companion study to the ROCKstar study, which investigated the drug in individuals who had cGVHD who received 2 to 5 prior lines of therapy. The ROCKstar study was a phase 2 clinical trial in 132 individuals. Investigators reported that treatment with 200 mg daily resulted in a response in 74% of patients, including those who were refractory to steroids, ruxolitinib, and ibrutinib, according to the study.1,2
In the current study, investigators evaluated the drug at the same daily dosage or twice daily in 20 individuals with oral cGVHD aged 21 to 77 years with 2 to 5 prior lines of systemic therapy. The primary endpoint was changes in local immune cellular profile and IL-17 signaling before and after 6 months of treatment. According to the abstract authors, individuals consented to additional collection of saliva, peripheral blood and biopsy of the skin, oral mucosa, and labial salivary glands at baseline and 6 months, or upon discontinuation if prior to 6 months. Matched biospecimens were blinded and analyzed, according to the authors.1
The investigators indicated that changes were identified in affected tissue after treatment, with responders demonstrating decreased oral mucosal collagen type III and I as overall or oral-specific National Institutes of Health response criteria, respectively, the results showed. Additionally, the investigators reported that immune cells, which included CD3+ and CD4+, also decreased in frequency for all patients. IL-17 also decreased in oral mucosa and salivary glands from all individuals, according to the authors of the abstract.1
Furthermore, individuals who received the drug once daily experienced decreases in both collagen type I and a drop in IL-17+ cells in oral mucosa, which was not evident in the twice daily arm. The study authors also said that fewer trends were noted in skin, though there were lower numbers of innate lymphoid cells identified in all individuals after treatment, according to the results. There were also increases in frequency of CD4+ T regulatory cells in the peripheral blood mononuclear cells and drops in salivary TGF-beta-1 post-treatment, according to the abstract authors.1
Reference
Sharma R, Holtzman NG, Cutler C, Mehta RS, et al. Poster Session: 357 - Effector Site Immune Dynamics in Refractory Chronic Graft-Versus-Host Disease: A Rockstar Trial Companion Study after Belumosudil Treatment. Tandem Meetings Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR. February 22, 2024. Accessed March 5, 2024. https://tandem.confex.com/tandem/2024/meetingapp.cgi/Paper/23473
Cutler C, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study [published correction appears in Blood. 2022 Mar 17;139(11):1772]. Blood. 2021;138(22):2278-2289. doi:10.1182/blood.2021012021
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