A Phase II Study to Determine the Safety and Efficacy of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase (IDO) Enzyme INCB024360 in Patients with Myelodysplastic Syndromes

Publication date: Available online 20 December 2018Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Rami S. Komrokji, Sheng Wei, Adam W. Mailloux, Ling Zhang, Eric Padron, David Sallman, Jeffrey E. Lancet, Sara Tinsley, Lisa A. Nardelli, Javier Pinilla-Ibarz, Pearlie K. Epling-Burnette, Alan F. ListAbstractINCB024360 is an oral inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO) which catalyzes the degradation of tryptophan (Trp) to Kynurenine (Kyn). Preclinical data suggest that IDO1 inhibition by INCB024360 will increase T cell proliferation, and decrease T regulatory cells and myeloid derived suppressor cells (MDSC) suppressive activity. We conducted a phase II study to explore activity and pharmacodynamics of INCB024360 in MDS patients. All patients were treated with 600 mg oral twice a day for at least 16 weeks. Fifteen patients were enrolled. The median age was 72 years, The IPSS risk was low 27% (4), intermediate-1 47% (7) and intermediate-2 27% (4). All patients had prior azacitidine. The best response was stable disease in 12 (80%) and progressive disease in 3 (20%) patients. The treatment was relatively well tolerated. One patient developed hypothyroidism and adrenal insufficiency (grade 2) and one patient had low testosterone level. The mean IDO expression was 39% at baseline and 26% after treatment (n=9, p 0.4). The mean BFU-E changed from 72 to 191 colonies/106 (n=5, p value 0.036) and the mean CFU GM from 62 to180 colonies/106 (n=6, p 0.5). The mea...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research