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419 Pharmacodynamic biomarkers demonstrate T-cell activation in patients treated with the oral PD-L1 inhibitor INCB086550 in a phase 1 clinical trial by Piha-Paul, Sarina ;Mitchell, Tara ;Sahebjam, Solmaz ;Mehnert, Janice ;Karasic, Thomas ;O’Hayer, Kevin ;Geschwindt, Ryan ;Spitz, Susan ;Liu, Hao ;Bendell, Johanna is a Medicine article available to read on EtoBox.

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Background Pharmacological blockade of the PD-1:PD-L1 interaction with monoclonal antibodies (mAbs) has shown durable clinical responses and overall survival benefit in a variety of malignancies.1 2 Importantly, the most meaningful responses have been associated with enhancement of the antitumor effector functions of T cells as evidenced by increased peripheral T-cell proliferation, infiltration of T cells in tumors, together with increased expression of key interferon-γ (IFNγ) pathway genes, including CXCL9, CXCL10, and granzyme B in both biopsy and peripheral blood samples.3 4 To date, available therapies targeting this pathway are mAbs, but the potential advantages of a small molecule, orally administered, direct antagonist of PD-1:PD-L1 binding have led to the development of INCB086550. INCB086550 is being evaluated in a phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with solid tumors. This preliminary report describes peripheral pharmacodynamic activity. Methods Peripheral blood was collected at baseline and at multiple time points posttreatment from 16 patients treated with INCB086550 QD (100, 200 mg) or BID (200, 400 mg

Who reads 419 Pharmacodynamic biomarkers demonstrate T-cell activation in patients treated with the oral PD-L1 inhibitor INCB086550 in a phase 1 clinical trial?

Author

Piha-Paul, Sarina ;Mitchell, Tara ;Sahebjam, Solmaz ;Mehnert, Janice ;Karasic, Thomas ;O’Hayer, Kevin ;Geschwindt, Ryan ;Spitz, Susan ;Liu, Hao ;Bendell, Johanna

Publisher

BMJ Publishing Group Ltd

Published

2020

Language

EN

Field

Medicine (Health Sciences)