A pivotal trial designed to assess KD025 for patients with pretreated chronic graft-versus-host disease met its primary endpoint of overall response rate, according to results from a planned interim analysis.
KD025 (Kadmon Holdings) is a selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2). The ROCK2 signaling pathway modulates inflammatory response.
The ongoing, open-label ROCKstar trial includes adults and adolescents with chronic GVHD who received at least two previous lines of systemic therapy. The FDA granted breakthrough therapy and orphan drug designations to KD025 for these indications.
Researchers randomly assigned 66 patients to receive KD025 dosed at 200 mg daily. The other 66 patients received KD025 dosed at 200 mg twice daily.
To meet statistical significance, the lower bound of the 95% CI for ORR had to exceed 30%.
Topline results from the interim analysis — performed 2 months after enrollment completion — showed ORRs of 64% (95% CI, 51-75) among patients assigned 200 mg daily and 67% (95% CI, 54-78) among those assigned 200 mg twice daily.
“The response rates observed are particularly impressive since this study is being conducted in a real-world population with severe disease, supporting the potential role of KD025 [for patients with chronic GVHD] who are in need of effective and well-tolerated therapies,” study investigator Corey Cutler, MD, MPH, FRCPC, associate professor of medicine at Harvard Medical School and medical director of the adult stem cell transplantation program at Dana-Farber Cancer Institute, said in a Kadmon-issued press release.
The primary analysis — planned for 6 months after enrollment completion — will be conducted in the first quarter of 2020. This analysis will include updated safety data, updated ORR data and results related to secondary endpoints, including duration of response, changes to corticosteroid dose and quality of life.
At the interim analysis, KD025 appeared well-tolerated, and researchers observed no unexpected adverse events.
“We are extremely pleased with the outcomes of the interim analysis, which showed that KD025 has already greatly exceeded the threshold for success in this pivotal trial,” Harlan W. Waksal, MD, president and CEO of Kadmon, said in the release. “We look forward to sharing these results with the FDA.”
A regulatory filing is expected in 2020, Waksal said.