Phase III GRAVITAS-301 Study Fails to Meet Primary Endpoint of Improved Overall Response

January 6, 2020

The study evaluating itacitinib in combination with corticosteroids in patients with treatment-naïve acute graft-versus-host disease did not produce statistically significant results.

The phase III GRAVITAS-301 study evaluating itacitinib in combination with corticosteroids in patients with treatment-naïve acute graft-versus-host disease (GVHD) did not meet the primary endpoint of improving overall response rate (ORR), according to Incyte, the agent’s manufacturer.

Though itacitinib added to corticosteroids improved the ORR in patients with treatment-naïve acute GVHD, the difference versus placebo plus corticosteroids was not statistically significant.

“The result of this study is disappointing. However, we remain committed to building on the success of the REACH program for ruxolitinib (Jakafi), which showed positive results in steroid refractory acute GVHD,” Steven Stein, MD, chief medical officer at Incyte, said in a press release. “Additionally, we will continue to study the role of JAK inhibition in chronic GVHD and in the prophylactic setting, as we seek to develop treatments for patients with this debilitating and often fatal disease.”

In the randomized, double-blind cohort of 439 participants, patients received either itacitinib or placebo plus prednisone and methylprednisolone. At day 28, the ORR for itacitinib in combination with corticosteroids compared to placebo plus corticosteroids was 74.0% vs 66.4%, respectively (= 0.08). Additionally, there was no difference observed in non-relapse mortality (NRM) at month 6 between the treatment and placebo arms (the study’s key secondary endpoint).

The safety profile observed in GRAVITAS-301 was consistent with previous observations in studies of itacitinib in combination with corticosteroids. The most commonly reported adverse events were thrombocytopenia (34.9% for itacitinib vs 34.7% for placebo) and anemia (29.8% vs. 25%, respectively). 

Investigators will be informed of the results and Incyte will work with them to appropriately conclude the study in a manner consistent with the best interest of each patient, according to the company. 

Itacitinib is a novel and selective JAK1 inhibitor that is currently still undergoing clinical study for the first-line treatment of patients with acute and chronic GVHD. 

Data from this study will be submitted for presentation at an upcoming scientific meeting.

Reference:

Incyte Announces Results of Phase 3 Study of Itacitinib in Patients with Treatment-Naïve Acute Graft-Versus-Host Disease [news release]. Wilmington, Delaware. Published January 2, 2020. investor.incyte.com/news-releases/news-release-details/incyte-announces-results-phase-3-study-itacitinib-patients. Accessed January 6, 2020.