RGI-2001 for aGvHD prophylaxis: Results from a phase IIb trial

A phase IIb trial (NCT04014790) assessed the safety and efficacy of RGI-2001 – a glycolipid that activates invariant natural killer T (NKT) cells and stimulates regulatory T (Treg) cell proliferation – in combination with standard calcineurin inhibitor (CNI)-based graft-versus-host disease (GvHD) prophylaxis for prevention of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). RGI-2001 was infused in combination with tacrolimus + methotrexate in 49 patients; results were published by DeFilipp et al. in Blood. 

Key data: The cumulative incidence of Grade 2–4 aGvHD and Grade 3–4 aGvHD was 24.9% and 4.1%, respectively, by Day 100. Grade ≥3 treatment-related adverse events occurred in 32.7% of patients, including decreased appetite, leukopenia, thrombocytopenia, and stomatitis. There were no cases of primary or secondary graft failure. The NKT and Treg populations increased post-HSCT, consistent with the proposed RGI-2001 mechanism of action.

Key learning: The findings demonstrate that RGI-2001 in combination with CNI-based prophylaxis was well tolerated and associated with low rates of aGvHD, supporting strategies that target NKT and Treg cells for aGvHD prophylaxis in patients receiving allo-HSCT.