Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors.
Auteurs
Jung KH, LoRusso PM, Burris HA, Gordon MS, Bang YJ, Hellmann MD, Cervantes A, Ochoa de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott DF, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey KM, Mahrus S, Morley R, Pirzkall A, Davis SL
Résumé
IDO1 induces immune suppression in T cells through L-tryptophan (Trp) depletion and kyneurinine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T-cells and hyperactivating Tregs. Navoximod is an investigational small molecule inhibitor of IDO1. This Phase I study evaluated safety, tolerability, PK and PD of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer.
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