Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Monoclonal, Humanized
/ administration & dosage
Female
Glucocorticoid-Induced TNFR-Related Protein
/ agonists
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Male
Melanoma
/ drug therapy
Middle Aged
Neoplasms
/ drug therapy
Transcriptome
Young Adult
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 04 2021
01 04 2021
Historique:
received:
23
07
2020
revised:
16
09
2020
accepted:
15
12
2020
pubmed:
24
12
2020
medline:
11
3
2022
entrez:
23
12
2020
Statut:
ppublish
Résumé
In this first-in-human phase I study (NCT02132754), we explored MK-4166 [humanized IgG1 agonist mAb targeting glucocorticoid-induced TNF receptor (GITR)] with and without pembrolizumab in advanced solid tumors. MK-4166 was tested alone (0.0015-900 mg i.v. every 3 weeks for four doses) or with pembrolizumab (200 mg i.v. every 3 weeks for ≤35 doses) in patients with metastatic solid tumors (dose escalation/confirmation) and advanced melanoma (expansion). Primary objectives were to evaluate the safety and tolerability and establish the MTD of MK-4166. Exploratory endpoints were objective response rate (ORR) and T cell-inflamed gene expression profile (GEP) analysis using RNA from baseline tumor samples. A total of 113 patients were enrolled [monotherapy, MK-4166 900 mg i.v. every 3 weeks as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naïve melanoma.
Identifiants
pubmed: 33355238
pii: 1078-0432.CCR-20-2886
doi: 10.1158/1078-0432.CCR-20-2886
pmc: PMC9094061
mid: NIHMS1798197
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Glucocorticoid-Induced TNFR-Related Protein
0
Immune Checkpoint Inhibitors
0
pembrolizumab
DPT0O3T46P
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1904-1911Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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