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

Clinical Snapshot

Key Findings

• P Value: Not reported for efficacy endpoints

• Effect Size: 0% grade 3-4 acute GVHD, 6% moderate/severe chronic GVHD, 0% relapse at 1 year

• Primary Outcome: Target pathway inhibition achieved with 75 mg twice daily VIC-1911 dose

• Nnt Or Sensitivity: 94% one-year overall survival (15/16 patients)

• Confidence Interval: Not reported

Clinical Application

Requires specialised transplant centres with Aurora kinase inhibitor availability and monitoring capabilities Would require TGA approval for VIC-1911; applicable to major transplant centres in Australia with established PTCy protocols Adults aged 18-60 undergoing myeloablative allogeneic HCT with suitable donors

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 <54% phosphorylated histone H3 serine 10 expression in CD4+ T cells by day +21. Preclinical models show that combining SIR with AURKA inhibition suppresses signaling downstream of CD28, enhancing GVHD prevention while leveraging the antileukemia activity of AURKA inhibition. In the phase 1 trial, the optimal VIC-1911 dose achieving target pathway inhibition without dose-limiting toxicities was 75 mg twice daily. Clinical outcomes included no grade 3 to 4 acute GVHD through day 180 (0%) and low rates of moderate/severe chronic GVHD (6%) and relapse (0%) through 1 year (5/16 received maintenance). The 1-year overall survival for this cohort was 94%. VIC-1911 at 75 mg twice daily, combined with PTCy and SIR, effectively suppressed AURKA activity, offering promising GVHD and relapse prevention with a favorable safety profile and promising early clinical outcomes. The trial was registered at www.clinicaltrials.gov as NCT05120570.

References

1. 1.Holtan, S. G., Grover, P., Walton, K., El Jurdi, N., Quinones, V., Maakaron, J. E., Juckett, M. B., Bachanova, V., Hou, J. H., Terezakis, S., Myers, T. J., Paradiso, L. J., DeFor, T. E., Cao, Q., & Betts, B. C. (2026). Targeting Aurora kinase A to prevent GVHD and relapse after myeloablative allogeneic hematopoietic cell transplantation. Blood Advances. https://doi.org/10.1182/bloodadvances.2025017360