The phase III GRAVITAS-301 clinical trial evaluating itacitinib plus corticosteroids in patients with treatment-naïve acute graft-versus-host disease (GVHD) did not produce statistically significant results.1
GVHD is a life-threatening complication associated with allogeneic haematopoietic stem cell transplantation (HSCT). The efficacy of itacitinib (a JK1 inhibitor) alone or in combination with corticosteroids was recently evaluated for initial treatment of acute GVHD.
The double-blind, international, phase III study GRAVITAS-301 enrolled 439 participants at 129 hospitals across 19 countries. Adults (18+) who had previously received allogeneic HSCT, developed grade 2-4 acute GVHD and received at least two days of corticosteroids were eligible for enrolment. Participants were randomised to either receive itacitinib (200 mg) or a placebo in addition to corticosteroids. The study’s primary endpoint was the overall response rate (ORR) at 28 days.
On day 28, the ORR with itacitinib plus corticosteroids was not statistically higher than the ORR in the placebo plus corticosteroids group (74% vs 66.4%, p=0.08). Moreover, no differences were observed in non-relapse mortality at six months between the treatment arms. Adverse events (grade 3 or higher) were seen in both itacitinib (86%) and placebo (82%) groups, with the most commonly observed AEs being thrombocytopenia (34.9% for itacitinib vs 34.7% for placebo) and anaemia (29.8% vs 25%, respectively).
The primary endpoint of the phase III GRAVITAS study evaluating itacitinib + corticosteroids in GVHD patients did not meet the primary endpoint of improving ORR.