Feb 2019 Clinical cancer research : an official journal of the American Association for Cancer Research

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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