EBMT 2018 | A phase II study to evaluate the safety, tolerability, and activity of KD025 in subjects with chronic GvHD

The 44^th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) took place in Lisbon, Portugal, on March 18-21 2018. On Wednesday March 21^st an oral abstract session was held on clinical GvHD. An abstract was presented during this session titled “A phase 2 open-label trial of kd025-208 for steroid-dependent chronic graft-versus-host disease (cGvHD)” by Madan Jagasia from Vanderbilt University Medical Center, Nashville, TN, USA. In the summary below, data from the live session at EBMT is used and therefore may supersede information in the pre-published Abstract.

Jagasia started his talk by introducing an ongoing open-label, dose-escalation phase II study (NCT02841995) investigating KD025, an oral ROCK2-selective inhibitor, in patients with steroid-dependent or refractory cGVHD. KD025 may reduce inflammation and fibrosis in cGvHD by downregulating Tfh and Th17 cells as well as upregulating regulatory T cells.

In total, 33 patients were enrolled and were divided into two groups receiving 200mg QD (Cohort 1, n= 17), 200mg BID (Cohort 2, n = 16). The key endpoints included overall complete and partial response rate, safety, and duration of response. Patients in Cohorts 1 and 2 had completed a median of three and two prior lines of cGVHD therapy. The most frequently involved organs in Cohorts 1 and 2, respectively, were eyes (82%, 69%), skin (76%, 75%), mouth (76%, 69%), joints (71%, 69%), and lung (24%, 44%). Forty-seven percent (47%) of patients in Cohort 1 and 69% in Cohort 2 had involvement of more than four organs. Treatment duration was 53 weeks for cohort 1 and 38 weeks for cohort 2.

Key findings:

• Safety
  • Treatment related > grade 3 adverse events (AEs) included elevated GGT, AST/ALT, anemia, dyspnea
    • Cohort 1: 12%
    • Cohort 2: 25%
  • The most common AEs included elevated AST/ALT levels, anemia, elevated GGT levels, URTI, diarrhea, nausea
• Efficacy
  • ORR was 65% in Cohort 1 and 69% in Cohort 2
  • Responses were rapid: 68% of responders achieved a response at the first eight weeks of treatment
• Corticosteroid and tacrolimus dose reductions
  • Median corticosteroid dose (mg/kg/day) reductions while on study:
    • Cohort 1: reduced with 40%
• • • Cohort 2: reduced with 26%
  • Tacrolimus dose reductions:
    • Cohort 1: 83% had reductions
    • Cohort 2: 83% had reductions

In summary, Jagasia stated that “treatment with KD025 was well-tolerated and no treatment related SAEs occurred.” Approximately two-thirds of patients with steroid-dependent or refractory cGvHD achieved a clinical response. There was no apparent increased risk of infection observed with KD025. Treatment in all cohorts is ongoing.