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Updated results from a phase 2 trial showed that treatment of chronic graft-vs-host disease (cGVHD) with belumosudil was well tolerated and resulted in high overall response rates (ORR) across key patient subgroups. Responses were durable and clinically meaningful.
The findings were presented by Corey Cutler, MD, of Dana-Farber Cancer Institute (Boston, MA), during the European Hematology Association (EHA) 2021 Virtual Congress.
ROCKstar (KD025-213; ClinicalTrials.gov Identifier: NCT03640481) is a phase 2, open-label, randomized, multicenter study to evaluate the efficacy and safety of belumosudil (previously called KD025) in patients with cGVHD after ≥2 prior lines of systemic therapy.
Belumosudil inhibits the protein kinase ROCK2, a key regulator of immune-mediated inflammatory and fibrotic signaling. Patients with cGVHD were randomized to receive 200 mg of belumosudil once (QD; n=66) or twice daily (BID; n=66) and were stratified according to cGVHD severity and prior ibrutinib use. The primary endpoint was the investigator-assessed ORR.
The median age of patients was 56 years (range, 21-77). Patients had received a median of 3 prior lines of therapy. The median time from cGVHD diagnosis was 29 months (range, 2-162). Among all patients, 67% had severe cGVHD; 34% had prior ibrutinib use; 52% had ≥4 organs involved; and 72% were refractory to line of therapy prior to enrollment.
Belumosudil resulted in clinically meaningful outcomes with a 75% ORR across the treatment arms; the ORR was 74% (95% CI, 60-83) in the QD arm and 77% (95% CI, 65-87) in the BID arm. ORRs were consistent across key subgroups, including ≥4 organs involved at baseline (71%), disease severity (severe, 74%; not severe, 77%), prior ibrutinib use (74%), prior ruxolitinib use (68%), number of prior lines of systemic therapy (≥4, 72%; <4, 78%), and duration of cGVHD prior to enrollment (>50th percentile, 68%; ≤50th percentile, 82%). Complete responses were observed in all organ systems.
“We noted complete responses in all organs that were treated, and at least 7 [patients] have had a true complete response in terms of their overall responses and all of the organs that they had involved,” Dr Cutler said.
Overall, 44% of patients remained on therapy for more than a year. The median DOR was 54 weeks, and 60% of responders maintained responses for ≥20 weeks.
Corticosteroids were completely discontinued in 21% of patients, and corticosteroid dose reductions were made in 64% of patients. Clinically meaningful improvement in quality of life was reported by 60% of patients (defined as a ≥7-point reduction in the Lee cGVGD symptom scale score).
Belumosudil was well tolerated. Adverse events (AEs) were similar in both treatment arms and consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Overall, the most common AEs (>20% patients) were fatigue (38%), diarrhea (33%), nausea (31%), cough (28%), upper respiratory infections (27%), dyspnea (25%), headache (24%), peripheral edema (23%), vomiting (21%), and muscle spasms (20%). On study, 8 patients died due to AEs (2 possibly related to belumosudil), and during long-term follow up (>28 days after last dose), 6 patients died.
“We can say that belumosudil was very well tolerated and achieved very meaningful clinical outcomes in this trial,” Cutler concluded.
Disclosure: Authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.
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Cutler C, Lee S, Arai S, et al. Belumosudil for chronic graft-versus host disease after 2 or more prior lines of therapy: the ROCKstar study (KD025-213). Presented at: European Hematology Association 2021 Virtual Congress; June 2021; Abstract S239.