Clinical Trials of Itacitinib for Chronic and Acute GVHD

Transcript:

Yi-Bin A. Chen, MD: Itacitinib is another oral JAK inhibitor. It is thought to be much more JAK1 selective when compared with ruxolitinib. This is important because JAK1 and JAK2 are thought to conduct different pathways of signaling. JAK1 is thought to be much more inflammatory. JAK2 signaling is thought to be much more important for hematopoiesis. The logic of using a JAK1-selective inhibitor is that it will hopefully provide the same effects in reducing inflammation and thus ameliorate graft-versus- host disease but have fewer effects on the cytopenias that are often seen with the use of ruxolitinib.

GRAVITAS-309 was designed as a phase III multicenter trial designed to study the role of itacitinib in the treatment of patients with a newly diagnosed graft-versus host disease. There are 2 phases in this trial. The first phase was to have a safety run-in for this population as well as to define the dose to move forward. That involved 20 patients, 10 were assigned to steroids plus itacitinib at 200 mg, and 10 were assigned to steroid plus itacitinib at 300 mg. This stage phase has completed accrual and we await the analysis of safety, of dose-limiting toxicities, pharmacokinetics, and the decision for picking a dose to move ahead with a larger study. The larger study will be a placebo-controlled randomized study comparing steroids with placebo versus steroids with itacitinib for the treatment of patients with newly diagnosed moderate to severe chronic graft-versus-host disease. The overall primary end point for this study will be 6-month response rate with the secondary end points including steroid taper as well as quality of life.

If itacitinib has a benefit for these patients, we hope that at 6 months patients who received itacitinib can meet all of these endpoints and that would truly be an advance in the treatment of chronic graft-versus-host disease.

GRAVITAS-301 is a phase III multicentered trial designed to study the role of itacitinib in the treatment of patients with a newly diagnosed acute graft-versus-host disease [GVHD]. Patients had to have overall grades 2 through 4, acute GVHD, to quality. They were then randomized to systemic corticosteroids with placebo, versus systemic corticosteroids with 200 mg of itacitinib daily.

The overall primary end point of this trial was day 28 response rate. And the key secondary end point included 6-month nonrelapsed mortality. If itacitinib were to have a benefit in this population, we would hope that at day 28 more patients had responded, specifically more complete responses. And we would hope that by 6 months less patients had died of acute graft-versus-host disease—related causes. This trial has finished accrual internationally and we look forward to seeing the results.

Transcript Edited for Clarity