First-in-man, first-in-class phase I study with the monopolar spindle 1 kinase inhibitor S81694 administered intravenously in adult patients with advanced, metastatic solid tumours.
Adult
Anemia
/ drug therapy
Antineoplastic Agents
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carcinoma, Renal Cell
/ drug therapy
Dose-Response Relationship, Drug
Fatigue
/ etiology
Humans
Kidney Neoplasms
/ drug therapy
Maximum Tolerated Dose
Neoplasms
/ drug therapy
MPS1
Monopolar spindle 1 kinase
Phase I
S81694
Spindle assembly checkpoint inhibitor
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
11
02
2022
revised:
28
03
2022
accepted:
01
04
2022
pubmed:
15
5
2022
medline:
14
6
2022
entrez:
14
5
2022
Statut:
ppublish
Résumé
S81694 is an inhibitor of monopolar spindle 1 kinase, a target expressed in proliferating cells. CL1-81694-001 was the first-in-human study aiming at identifying a safe dosing schedule in solid tumour patients. This trial was based on inter-individual dose-escalation of single agent S81694 in cohorts of ≥3 patients to assess the safety and tolerability and determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase II dose (RP2D), with S81694 given on days 1,8,15 of a 28-day cycle as 1-h infusion. 38 patients were treated at doses ranging from 4 to 135 mg/m S81694 can be administered safely as a single agent in adults with solid tumours on days 1,8,15 of a 28-day cycle up to a dose of 135 mg/m EudraCT number: 2014-002023-10; ISRCTN registry ISRCTN35641359.
Sections du résumé
BACKGROUND
S81694 is an inhibitor of monopolar spindle 1 kinase, a target expressed in proliferating cells. CL1-81694-001 was the first-in-human study aiming at identifying a safe dosing schedule in solid tumour patients.
PATIENTS AND METHODS
This trial was based on inter-individual dose-escalation of single agent S81694 in cohorts of ≥3 patients to assess the safety and tolerability and determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended phase II dose (RP2D), with S81694 given on days 1,8,15 of a 28-day cycle as 1-h infusion.
RESULTS
38 patients were treated at doses ranging from 4 to 135 mg/m
CONCLUSIONS
S81694 can be administered safely as a single agent in adults with solid tumours on days 1,8,15 of a 28-day cycle up to a dose of 135 mg/m
TRIAL REGISTRATION
EudraCT number: 2014-002023-10; ISRCTN registry ISRCTN35641359.
Identifiants
pubmed: 35567919
pii: S0959-8049(22)00170-8
doi: 10.1016/j.ejca.2022.04.001
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Banques de données
EudraCT
['2014-002023']
ISRCTN
['ISRCTN35641359']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-145Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.