@article{b8466102f2364554a7e6698942270db2,
title = "A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease",
abstract = "Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1–selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged $18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n 5 14; 300 mg, n 5 15) received $1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n 5 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.",
author = "Schroeder, {Mark A.} and {Jean Khoury}, H. and Madan Jagasia and Haris Ali and Schiller, {Gary J.} and Karl Staser and Jaebok Choi and Leah Gehrs and Arbushites, {Michael C.} and Ying Yan and Peter Langmuir and Nithya Srinivas and Michael Pratta and Perales, {Miguel Angel} and Chen, {Yi Bin} and Gabrielle Meyers and DiPersio, {John F.}",
note = "Funding Information: This study was funded by Incyte Corporation and received support from National Institutes of Health, National Cancer Institute grants P30-CA9184201 (J.F.D.), SPORE P50-CA171963-01 (J.F.D.), R35 1R35-CA210084 (J.F.D.), the Amy Strelzer Manasevit Research Program (Be The Match Foundation and the National Marrow Donor Program) (J.C.), and the Alvin J. Siteman Cancer Center Siteman Investment Program (Foundation for Barnes-Jewish Hospital Cancer Frontier Fund, National Cancer Institute Cancer Center Support Grant, P30 CA091842, and Barnard Trust) (J.C.). Funding Information: Conflict-of-interest disclosure: M.A.S. received honoraria and research funding from Incyte Corporation. H.J.K. served on an advisory board and received research funding from Incyte Corporation. M.J. received research funding from Therakos, Janssen, and Incyte Corporation. H.A. and G.J.S. received research funding from Incyte Corporation. K.S. served as a consultant for RiverVest and Kinetic River and is a coinventor on a patent related to CART therapy. J.C. received honorarium from Incyte Corporation, received research funding from Mallinckrodt Pharmaceuticals, and served as a consultant for Daewoong Pharmaceutical. M.C.A., Y.Y., P.L., N.S., and M.P. are employees and stockholders of Incyte Corporation. M.-A.P. received honoraria from AbbVie, Bellicum, Bristol-Myers Squibb, Incyte Corporation, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; served on data and safety monitoring boards for Servier and Medigene; served on scientific advisory boards for MolMed and NexImmune; and has received research support for clinical trials from Incyte Corporation, Kite/Gilead, and Miltenyl Biotec. Y.-B.C. served as a consultant for Incyte Corporation and Takeda and received research funding from Incyte Corporation and Novartis Pharmaceuticals. J.F.D. served on advisory boards for Incyte Corporation, CellWorks, Macrogenics, Amphivena, Arch, Rivervest, and Bioline and is a cofounder of Magenta Therapeutics and WUGen. The remaining authors declare no competing financial interests. Funding Information: Acknowledgments The authors thank Michael Howell, at Incyte Corporation, for assistance with biomarker and translational assessments. Writing assistance was provided by Jane Kovalevich, at Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group company, and funded by Incyte Corporation. The authors acknowledge the participating study sites and all participating patients. Publisher Copyright: {\textcopyright} 2020 by The American Society of Hematology",
year = "2020",
month = apr,
day = "28",
doi = "10.1182/bloodadvances.2019001043",
language = "English",
volume = "4",
pages = "1657--1669",
journal = "Blood Advances",
issn = "2473-9529",
number = "8",
}