Dr Lee on 3-Year Follow-Up Data From the ROCKstar Trial of Belumosudil in cGVHD

Stephanie Lee, MD, MPH, professor, associate director, Clinical Research Division, David and Patricia Giuliani/Oliver Press Endowed Chair, Cancer Research, Fred Hutchinson Cancer Center, discusses 3-year follow-up data from the phase 3 ROCKstar Study (NCT03640481) evaluating belumosudil (Rezurock) for chronic graft-vs-host disease (cGVHD), highlighting the significance of these findings.

In July, 2021, the FDA approved the oral selective rho-associated coiled-coil–containing protein kinase-2 inhibitor belumosudil for the treatment of adult and pediatric patients 12 years and older with cGVHD following progression on 2 or more prior lines of systemic therapy. The regulatory decision was supported by safety and efficacy data from the ROCKstar trial (KD025-213). Previously reported data showed that the agent elicited a high overall response rate at doses of 200 mg per day and 200 mg twice daily after a median follow-up of 14 months.

Given the evolving landscape of cGVHD treatment and the need for more extended follow-up data, investigators sought to provide a comprehensive assessment of the treatment's efficacy and safety over a 3-year period. This extended follow-up was crucial to ascertain whether these initial results would persist over time.

The open-label, multicenter trial included 152 patients with cGVHD who had previously received 2 to 5 lines of systemic therapy, including 20 unreported participants enrolled in a subsequent biomarker study. Patients in the modified intent-to-treat (mITT) population received one of the 2 belumosudil dose levels.

Extended follow-up data from the study were presented at the 2024 Transplantation & Cellular Therapy Meetings, demonstrating prolonged efficacy and minimal toxicity with belumosudil, Lee begins. A 3-year overall response rate (ORR) of 74% was seen with the 200-mg once-daily arm, and an overall response rate (ORR) of 76% was observed in the 200-mg twice-daily arm. Notably, response rates remained stable with the increased population size and belumosudil exposure, with consistent responses observed across all organ systems. The failure free-survival (FFS) rates with belumosudil were 44.1% in the mITT population, and 51.8% in the responder population. Additionally, the overall duration of response (DOR) with belumosudil increased from 51.4% in the original analysis to 77.1% in the follow-up analysis, Lee states.

Despite additional exposure to belumosudil, no new safety signals were identified. Overall, 21.0% and 13.2% of participants discontinued treatment due to cGVHD progression or toxicities, respectively. However, treatment discontinuation rates decreased due to progression of cGVHD or AEs each year after follow-up, Lee explains.

These data are particularly encouraging for community oncologists who may have limited exposure to these newer treatment options. Ultimately, the study underscores the potential for patients to maintain responses to the drug over an extended period without experiencing increased toxicities, she concludes.