Pharmacodynamic assessment of INCB024360, an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), in advanced cancer patients.
2017
2500^ Background: The ineffectiveness of the immune system to control tumor growth is, in part, a result of immunosuppression imposed by negative regulatory mechanisms. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme that catabolizes the first and rate-limiting step in the degradation of the essential amino acid tryptophan (Trp) to kynurenine (Kyn), has been shown preclinically to play an important role in tumor-mediated immunosuppression. In cancer patients (pts), elevated IDO1 levels are associated with poor prognosis and shortened survival in a number of tumor types. Here we describe the pharmacodynamic (PD) assessment of INCB024360, a novel inhibitor of IDO1. Methods: Plasma samples were obtained from consented pts in study INCB 24360-101, a phase I dose-escalation study in patients with advanced malignancies. Trp and Kyn levels in plasma were determined by LC/MS/MS. IDO1 activity in activated peripheral blood cells was also monitored. Results: Using anti-IDO1 specific antisera and archived tumor samp...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
23
Citations
NaN
KQI