Targeting Aurora kinase A to prevent GVHD and relapse after myeloablative allogeneic hematopoietic cell transplantation

ABSTRACT: The success of posttransplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has driven efforts to optimize partner therapies that balance GVHD and relapse prevention. We report phase 1 dose-finding results of PTCy, sirolimus (SIR), and VIC-1911, a selective oral Aurora kinase A (AURKA) inhibitor, after myeloablative allogeneic hematopoietic cell transplantation (allo-HCT). Results from murine and in vitro studies informed the development of the novel drug combination. In the phase 1 trial, patients aged 18 to 60 years received myeloablative conditioning, followed by PTCy (50 mg/kg; days +3/+4), SIR (from day +5; target 8-12 ng/mL), and VIC-1911 (25, 50, or 75 mg twice daily; days +5 to +45). The primary end point was achieving