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.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
B7-H1 Antigen
/ antagonists & inhibitors
Biomarkers, Tumor
Humans
Imidazoles
/ administration & dosage
Indoleamine-Pyrrole 2,3,-Dioxygenase
/ antagonists & inhibitors
Indoles
/ administration & dosage
Magnetic Resonance Imaging
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Neoplasms
/ diagnosis
Tomography, X-Ray Computed
Treatment Outcome
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 06 2019
01 06 2019
Historique:
received:
28
08
2018
revised:
06
12
2018
accepted:
12
02
2019
pubmed:
17
2
2019
medline:
7
7
2020
entrez:
17
2
2019
Statut:
ppublish
Résumé
IDO1 induces immune suppression in T cells through l-tryptophan (Trp) depletion and kynurenine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T cells and hyperactivating regulatory T cells (Treg). Navoximod is an investigational small-molecule inhibitor of IDO1. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. The study consisted of a 3+3 dose-escalation stage ( Patients ( The combination of navoximod and atezolizumab demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Although activity was observed, there was no clear evidence of benefit from adding navoximod to atezolizumab.
Identifiants
pubmed: 30770348
pii: 1078-0432.CCR-18-2740
doi: 10.1158/1078-0432.CCR-18-2740
pmc: PMC7980952
mid: NIHMS1675625
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
IDO1 protein, human
0
Imidazoles
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Indoles
0
atezolizumab
52CMI0WC3Y
navoximod
926SHL95NC
Banques de données
ClinicalTrials.gov
['NCT02471846']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3220-3228Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
Références
Trends Immunol. 2016 Mar;37(3):193-207
pubmed: 26839260
Mod Pathol. 2018 Oct;31(10):1513-1522
pubmed: 29802358
Trends Cancer. 2018 Jan;4(1):38-58
pubmed: 29413421
Nature. 2014 Nov 27;515(7528):563-7
pubmed: 25428504
Lancet Oncol. 2019 Aug;20(8):1083-1097
pubmed: 31221619
Eur J Cancer. 2017 May;76:167-182
pubmed: 28324751
Sci Transl Med. 2010 May 19;2(32):32ra36
pubmed: 20484731
Immunity. 2009 Dec 18;31(6):974-85
pubmed: 20064452
Lancet. 2017 Jan 21;389(10066):255-265
pubmed: 27979383
Int Immunopharmacol. 2017 Jun;47:70-77
pubmed: 28365507
Mod Pathol. 2018 Aug;31(8):1282-1290
pubmed: 29559741
Nat Med. 2003 Oct;9(10):1269-74
pubmed: 14502282