A phase 1 dose-escalation study of checkpoint kinase 1 (CHK1) inhibitor prexasertib in combination with p38 mitogen-activated protein kinase (p38 MAPK) inhibitor ralimetinib in patients with advanced or metastatic cancer.


Journal

Investigational new drugs
ISSN: 1573-0646
Titre abrégé: Invest New Drugs
Pays: United States
ID NLM: 8309330

Informations de publication

Date de publication:
08 2020
Historique:
received: 09 08 2019
accepted: 22 10 2019
pubmed: 11 11 2019
medline: 10 9 2021
entrez: 11 11 2019
Statut: ppublish

Résumé

Purpose The primary objective was to determine the recommended Phase 2 dose (RP2D) of checkpoint kinase 1 inhibitor, prexasertib, in combination with the p38 mitogen-activated protein kinase inhibitor, ralimetinib, which may be safely administered to patients with advanced cancer. Methods This Phase 1, nonrandomized, open-label, dose-escalation study of prexasertib+ralimetinib included patients with advanced and/or metastatic cancer, followed by a planned cohort expansion in patients with colorectal or non-small-cell lung cancer with KRAS and/or BRAF mutations. Intravenous prexasertib was administered at 60 mg/m

Identifiants

pubmed: 31707688
doi: 10.1007/s10637-019-00873-6
pii: 10.1007/s10637-019-00873-6
doi:

Substances chimiques

Antineoplastic Agents 0
Imidazoles 0
Protein Kinase Inhibitors 0
Pyrazines 0
Pyrazoles 0
Pyridines 0
prexasertib 0
ralimetinib 73I34XW4HD
Checkpoint Kinase 1 EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24

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

1145-1155

Auteurs

Johanna C Bendell (JC)

Sarah Cannon Research Institute, Tennessee Oncology PLLC, 250 25th Avenue N, Suite 200, Nashville, TN, 37203, USA. jbendell@tnonc.com.

Helge G Bischoff (HG)

Department of Thoracic Oncology, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg University Hospital, 69126, Heidelberg, Germany.

Jimmy Hwang (J)

Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.

Hans Christian Reinhardt (HC)

University of Cologne, University Hospital Cologne, Clinic I for Internal Medicine, Weyertal 115B, 50931, Cologne, Germany.
University of Cologne, Center for Molecular Medicine Cologne, Rober Koch Str. 21, 50931, Cologne, Germany.

Thomas Zander (T)

Clinic I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.

Xuejing Wang (X)

Eli Lilly and Company, Indianapolis, IN, USA.

Scott Hynes (S)

Eli Lilly and Company, Indianapolis, IN, USA.

Celine Pitou (C)

Eli Lilly and Company, Indianapolis, IN, USA.

Robert Campbell (R)

Eli Lilly and Company, Indianapolis, IN, USA.

Philip Iversen (P)

Eli Lilly and Company, Indianapolis, IN, USA.

Daphne L Farrington (DL)

Eli Lilly and Company, Indianapolis, IN, USA.
Verastem Oncology, Needham, MA, USA.

Katherine Bell-McGuinn (K)

Eli Lilly and Company, Indianapolis, IN, USA.

Michael Thomas (M)

Department of Thoracic Oncology, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg University Hospital, 69126, Heidelberg, Germany.

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Classifications MeSH