Belumosudil Impresses in cGVHD, FDA Submission Started

Madan Jagasia, MD, MBBS

Belumosudil (KD025) continued to show clinically meaningful and statistically significant overall response rates (ORRs), in patients with chronic graft-versus-host disease (cGVHD) who have received ≥2 prior lines of systemic therapy, according to topline results from the primary analysis of the phase 2 ROCKstar trial.

At the 200-mg once-daily dose, belumosudil elicited an ORR of 73% (95% CI, 60%-83%; P <.0001), and the 200-mg twice-daily schedule led to a 74% ORR (95% CI, 62%-84%; P <.0001) in this patient population. Kadmon Holdings, Inc., the developer of belumosudil, reported in a press release that responses occurred in key subgroups of patients and were observed by investigators across all organ systems.

The median response duration has not yet been reached, with 49% of responding patients maintaining their response for ≥20 weeks.

The primary analysis data sustained the high level of activity shown at the interim analysis. At the earlier assessment, the study met its primary ORR endpoint. Kadmon reported in a press release that it is submitting a new drug application for belumosudil to the FDA under the Real-Time Oncology Review pilot program.

"Treatment with belumosudil has demonstrated compelling results for this major unmet medical need. Importantly, belumosudil has been very well tolerated, which allows trial participants to stay on therapy and achieve meaningful responses," Madan Jagasia, MD, MS, MMHC, an investigator on the ROCKstar study and the ROCKstar Steering Committee chair, stated in the press release.

"These results demonstrate the potential of belumosudil to become a cornerstone of the cGVHD treatment paradigm, if approved, as it delivers meaningful and sustained benefits to patients with this serious condition," added Jagasia, professor of medicine, Vanderbilt University Medical Center; co-leader, Translational Research and Interventional Oncology; chief medical officer, Vanderbilt-Ingram Cancer Center."

In the ongoing, multicenter, open-label, phase 2 ROCKstar trial, belumosudil is being tested in adults and adolescents with cGVHD who have received ≥2 prior lines of systemic therapy. Patients were randomized 1:1 to receive belumosudil at either 200 mg daily (n = 66) or 200 mg twice daily (n = 66).

To be eligible for enrollment, patients must be ≥12 years old and have undergone allogenic hematopoietic stem cell transplant, previously received ≥2 lines of systemic therapy, receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening, have persistent cGVHD manifestations, a Karnofsky performance score ≥60 (if aged ≤16 years) or a Lansky performance score of ≥60 (if aged <16 years), and weigh ≥40 kg.

Those who are not on a stable dose or regimen of systemic cGVHD therapy for ≥2 weeks prior to screening, have histological relapse of the underlying disease or posttransplant lymphoproliferative disease at time of screening, and are currently being treated with ibrutinib (Imbruvica) are excluded from enrolling on the trial.

The primary end point is ORR; key secondary endpoints are duration of response, change in Lee Chronic GVHD Symptom Scale Score, response rate by organ system, partial or complete response rate, failure-free survival, overall survival, time to response, and time to next treatment.

Kadmon reported in the press release that the therapy has been well tolerated and adverse events were found to be consistent with what is expected in this patient population. “No cytomegalovirus infection or reactivation has been observed and no significant drug-related cytopenias have been reported,” the company added.

Cytokines (IL-21, IL-17) regulated by the ROCK2 signaling pathway play an integral role in the pathogenesis of cGVHD. Clinical research has demonstrated that inhibiting the ROCK2 pathway reduces the pathogenesis of cGVHD.

Kadmon Announces Positive Topline Results of Pivotal Trial of Belumosudil (KD025) in Chronic Graft-Versus-Host Disease. Published May 21, 2020. https://yhoo.it/2zTLXYu. Accessed May 21, 2020.