EHA 2018 | Updates from the KD025-208 study

KD025, a Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor, is being evaluated in an ongoing phase II trial (KD025-208, NCT02841995) in patients with chronic graft-versus-host disease (cGvHD). The previous results of this study have been reported by the GvHD Hub here. At the 23^rd Congress of EHA (European Hemtology Association), Stockholm, Sweden, updated results of the study were presented by Amandeep Salhotra from City of Hope National Medical Center, Duarte, CA, USA, on behalf of Madan Jagasia.

Patient characteristics:

• In total, 33 patients with cGvHD involvement across all organ systems were enrolled and divided into two cohorts (Cohort 1 [n = 17], Cohort 2 [n = 16])
• Median age
  • Cohort 1: 50 years (range, 20-63)
  • Cohort 2: 55 years (range, 30-75)
• Patients had cGvHD for a median of 18.9 months prior to KD025 treatment
• A median of 3 prior lines of cGVHD therapy was administered
• Cohort 1 received 200 mg QD of KD025
• Cohort 2 received 200 mg BID of KD025
• To date, six patients are active in Cohort 1 and five patients in Cohort 2

Key findings:  

• Median treatment duration: 70 weeks in Cohort 1 and 58 weeks in Cohort 2
• Safety
  • Most common adverse events (AEs)
    • Cohort 1: elevated AST/ALT (35%), diarrhea (35%), nausea (35%) anemia (29%), elevated GGT (24%)
    • Cohort 2: elevated GGT (31%), URTI (38%), anemia (25%), elevated AST/ALT (25%)
  • Most common grade > 3 AEs
    • Cohort 1: anemia (12%), elevated GGT (12%), hyperglycemia (12%)
    • Cohort 2: elevated GGT (19%), anemia, elevated ALT/AST
  • No patients have discontinued treatment due to infection
• Overall Response Rate (ORR)
  • ORR in Cohort 1: 65% (11/17)
  • ORR in Cohort 2: 69% (11/16)
  • 77% of patients across Cohorts 1 and 2 achieved responses by the first assessment (after 8 weeks of treatment)
• Responses across organ systems
  • CRs in upper GI, lower GI, esophagus, mouth, joints/fascia, skin, eyes and liver
  • In responders with ≥ 4 organs involved, 46% showed responses in ≥ 4 organs
• Corticosteroid and tacrolimus dose reduction
  • Cohort 1: 73% (8/11) of responders and 83% (5/6) of non-responders achieved dose reductions
  • Cohort 2: 55% (6/11) of responders and 60% (3/5) of non-responders achieved dose reductions
  • Five patients completely discontinued steroid use
  • 83% of patients were able to reduce the dose of tacrolimus

In summary, this study shows that KD025 is well-tolerated and can be a promising therapy choice for cGvHD patients providing favorable clinical outcomes, while minimizing AEs of high dose steroid therapy. Approximately two-thirds of steroid-dependent or refractory cGvHD patients had a clinical response.