Incyte said today that the first patient has been treated in a Phase III trial assessing itacitinib, its Janus kinase inhibitor 1 (JAK1), as a potential treatment for acute graft-versus-host disease (GVHD) in combination with corticosteroids.
The combination of itacitinib and corticosteroids is being compared with placebo and corticosteroids in the GRAVITAS-301 trial, which is designed to study itacitinib as a first-line treatment of acute GVHD patients.
GRAVITAS-301 (NCT03139604) will enroll approximately 430 patients 18 years or older who have undergone one allogeneic transplant from any donor and any donor source for a hematologic malignancy or disorders. The primary endpoint of the GRAVITAS-301 study is overall response rate (ORR) at day 28, defined as the proportion of subjects demonstrating a complete response, very good partial response, or partial response, Incyte said.
Key secondary endpoints of GRAVITAS-301 include nonrelapse mortality at month 6, defined as the proportion of subjects who died due to causes other than malignancy relapse, duration of response, and ORR at day 14, 56, and 100.
The study’s estimated primary completion date, or final data collection date for primary outcome measure, is April 2019, with the study set to be completed in March 2020, according to GRAVITAS-301’s page on ClinicalTrials.gov.
“The initiation of the GRAVITAS-301 trial represents an important milestone for Incyte as we continue to progress our clinical development portfolio, and we look forward to further evaluating the potential of itacinitib to address the unmet needs of patients with this potentially devastating condition,” Incyte CMO Steven Stein, M.D., said in a statement.
Itacitinib, also called INCB039110, is a novel, potent, and selective JAK1 inhibitor now under clinical study as a therapy for treatment naïve GVHD and non-small-cell lung cancer.
Itacitinib is not the only treatment Incyte is looking to develop for the disease. Last year, Incyte received the FDA’s breakthrough therapy designation for its drug Jakafi® (ruxolitinib) as a treatment for acute GVHD, and also has the agency’s Orphan Drug Designation for the disease.
Jakafi is already approved in the U.S. for treating myelofibrosis and polycthemia vera.
In December 2016, Incyte said the first acute GVHD patient had been treated with Jakafi in the pivotal Phase II REACH-1 trial (NCT02953678), which is assessing the drug in combination with corticosteroids. The study’s estimated primary completion date is March 2020, with the study completion date projected for June 2020.
No treatments are approved for either acute or chronic GVHD, which can occur after an allogeneic transplant. That could change later this year: The FDA is reviewing the supplemental New Drug Application (NDA) submitted by Pharmacyclics, an AbbVie company, and Johnson & Johnson’s Janssen Biotech for Imbruvica® (ibrutinib) as a treatment for chronic GVHD after failure of one or more lines of systemic therapy.
Imbruvica won FDA breakthrough therapy designation for chronic GVHD last year.
Imbruvica is already approved for some forms of non-Hodgkin’s lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including patients with 17p deletion; patients with mantle cell lymphoma (MCL) who have received at least one prior therapy; patients with Waldenström’s macroglobulinemia (WM); and patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Continued approval for MZL and MCL may hinge upon verification and description of clinical benefit in a confirmatory trial.
Another recent development spotlighted the challenge of successfully developing GVHD treatments. Last month, Shire transferred its Investigational New Drug (IND) application for the acute GVHD treatment candidate alpha-1 antitrypsin (G1-AAT IV) in the U.S. to Kamada, which is overseeing development in Europe. The transfer halted a Phase II/III study that saw a “slow recruitment rate” of patients—one of two reasons Kamada said Shire gave for the transfer, along with the biotech giant having other pipeline priorities.