A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ pharmacokinetics
Antineoplastic Agents, Immunological
/ pharmacokinetics
Breast Neoplasms
/ drug therapy
Female
Follow-Up Studies
Humans
Immunoconjugates
/ chemistry
Male
Maximum Tolerated Dose
Middle Aged
Neoplasms
/ drug therapy
Oligopeptides
/ pharmacokinetics
Prognosis
Receptor, Notch3
/ antagonists & inhibitors
Retrospective Studies
Tissue Distribution
Young Adult
ADC
Breast cancer
Notch3
PF-06650808
Safety
Solid tumors
Journal
Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
10
10
2018
accepted:
01
03
2019
pubmed:
20
3
2019
medline:
24
10
2020
entrez:
20
3
2019
Statut:
ppublish
Résumé
Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-agent PF-06650808 in 40 patients with advanced breast cancer (BC) and other solid tumors unselected for Notch3 expression. Primary endpoint was dose-limiting toxicity (DLT). PF-06650808 was administered intravenously every 3 weeks at a starting dose of 0.2 mg/kg, escalated up to 6.4 mg/kg following the modified continual reassessment method. An additional dose level, 2.0 mg/kg, was evaluated in patients with advanced, estrogen receptor-positive (ER
Identifiants
pubmed: 30887250
doi: 10.1007/s10637-019-00754-y
pii: 10.1007/s10637-019-00754-y
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Immunoconjugates
0
NOTCH3 protein, human
0
Oligopeptides
0
PF-06650808
0
Receptor, Notch3
0
Banques de données
ClinicalTrials.gov
['NCT02129205']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
120-130Références
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