Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
/ administration & dosage
Breast Neoplasms
/ drug therapy
Cell Proliferation
/ drug effects
Drug-Related Side Effects and Adverse Reactions
/ classification
Female
Humans
Immunologic Factors
/ administration & dosage
Lipopolysaccharide Receptors
/ genetics
Male
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
Receptor, Macrophage Colony-Stimulating Factor
/ antagonists & inhibitors
Receptors, IgG
/ genetics
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 11 2020
01 11 2020
Historique:
received:
08
03
2020
revised:
02
07
2020
accepted:
20
08
2020
pubmed:
28
8
2020
medline:
27
11
2021
entrez:
28
8
2020
Statut:
ppublish
Résumé
Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. Patients with advanced refractory metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) were treated with LY3022855 intravenously in 6-week cycles in cohorts: (A) 1.25 mg/kg every 2 weeks (Q2W); (B) 1.0 mg/kg on weeks 1, 2, 4, and 5; (C) 100 mg once weekly; (D)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. Thirty-four patients (22 MBC; 12 mCRPC) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14 LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two patients with MBC.
Identifiants
pubmed: 32847933
pii: 1078-0432.CCR-20-0855
doi: 10.1158/1078-0432.CCR-20-0855
pmc: PMC8519606
mid: NIHMS1740187
doi:
Substances chimiques
Antibodies, Monoclonal
0
Immunologic Factors
0
Lipopolysaccharide Receptors
0
Receptors, IgG
0
Receptor, Macrophage Colony-Stimulating Factor
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT02265536']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5609-5620Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA214785
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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