Oral ROCK2 inhibitor KD025 treatment after 2 months total remission rate (ORR)> 60%!

The 2020 ASBMT / CIBMTR Transplantation and Cell Therapy Annual Conference (TCT 2020) was held in Orlando, Florida, USA from February 19-23, 2020. The Research Center (CIBMTR) was jointly held and introduced the latest developments in basic science, translational research and clinical research in various fields of blood and bone marrow transplantation and cell therapy.

At this meeting, Kadmon Holdings Company released the latest data of ROCKstar (KD025-213, NCT03640481), a key clinical trial of oral selective Rho-associated coiled-coil protein kinase 2 (ROCK2) inhibitor KD025 in the treatment of chronic graft-versus-host disease (cGVHD) (For details, click: KD025-213 Interim Analysis – TCT 2020 Slides).

This is an ongoing open-label phase II study in adult and adolescent patients with cGVHD who have previously received at least 2 systemic therapies. In the study, patients were randomly assigned to two groups and received KD025 200 mg once daily and 200 mg twice daily, 66 patients in each group. In this study, if the lower limit of the 95% CI of the total response rate (ORR) exceeds 30%, statistical significance is achieved.

The results showed that in a mid-term analysis (October 2019) conducted 2 months after completion of patient enrollment, the study had reached the ORR endpoint. The data showed that the ORR of KD025 once daily 200 mg treatment group and twice daily 200 mg treatment group were 64% (95% CI: 51%, 75%, p 0010010 lt;0.0001), 67% (95% CI: 54%, 78%, p 0010010 lt;0.0001), the data has statistical significance and clinical significance.

The extended data provided at the meeting showed that after a median follow-up of 5 months, the ORR reported by each key subgroup was consistent with the previously reported mid-term analysis results, including: a subgroup of patients with 4 or more organs affected by cGVHD ( n = 69, ORR = 64%), a subgroup of patients who had previously received ibrutinib (irutinib, BTK inhibitor) (n = 45; ORR = 62%), and previously received ruxolitinib (ruzotinib, A subset of patients treated with JAK1 / JAK2 inhibitors (n = 37; ORR = 62%). Three patients achieved complete remission. Treatment responses were observed in all affected organ systems, including those with fibrotic diseases.

In the study, KD025 was well tolerated: adverse events were generally consistent with the expected adverse events observed in patients with cGVHD treated with corticosteroids, and no significant increase in infection risk was observed. Additional secondary endpoints, including duration of remission (DOR), reduced corticosteroid dose, failure-free survival (FFS), overall survival (OS), and Lee Symptom Scale (LSS) score reduction are continuing to mature and will Data obtained later in 2020.

KD025 chemical structure and mechanism of action.

Kadmon President and Chief Executive Officer Harlan W. Waksal, M.D., said: 0010010 quot;We are very satisfied with the mid-term results of this key trial of KD025 in cGVHD, which closely tracks the results of our earlier phase II study. KD025 is difficult in this A good response rate has been achieved in all subgroups of the treatment patient group. These patients have received four therapies before, and 73% of them did not respond to the last therapy. We plan to contact the US Food and Drug Administration in March 2020 (FDA) held a pre-NDA meeting and announced the top-line results of the main analysis of the trial in the second quarter of 2020. 0010010 quot;

KD025 is a selective oral inhibitor of Rho-associated coiled-coil protein kinase 2 (ROCK2), a signaling pathway that regulates immune responses and fibrosis pathways. KD025 inhibits the ROCK2 signaling pathway, down-regulates proinflammatory Th17 cells, increases regulatory T (Treg) cells, rebalances the immune response, and treats immune dysfunction. In addition to cGVHD, KD025 is undergoing a phase II clinical trial of adult diffuse skin systemic sclerosis (KD025-209). Previously, KD025 was granted Breakthrough Drug Qualification (BTD) and Orphan Drug Qualification (ODD) by the US Food and Drug Administration (FDA) for the treatment of cGVHD patients who have previously received at least two systemic treatments.

cGVHD is a common fatal complication after hematopoietic stem cell transplantation. In cGVHD, transplanted immune cells (grafts) attack the patient 0010010 #39;s cells (host), causing inflammation and fibrosis in multiple tissues such as skin, mouth, eyes, joints, liver, lungs, esophagus, and gastrointestinal tract. In the United States, there are currently about 14,000 patients with cGVHD, and about 5,000 new patients are added each year. (Bioon.com)