Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors.
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
ISSN: 1527-7755
Titre abrégé: J Clin Oncol
Pays: United States
ID NLM: 8309333
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
pubmed:
18
3
2020
medline:
3
2
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
Lifirafenib is an investigational, reversible inhibitor of B-RAF During dose escalation, adult patients with histologically/cytologically confirmed advanced solid tumors received escalating doses of lifirafenib. Primary end points were safety/tolerability during dose escalation and objective response rate in preselected patients with The maximum tolerated dose was established as 40 mg/d; dose-limiting toxicities included reversible thrombocytopenia and nonhematologic toxicity. Across the entire study, the most common grade ≥ 3 treatment-emergent adverse events were hypertension (n = 23; 17.6%) and fatigue (n = 13; 9.9%). One patient with Lifirafenib is a novel inhibitor of key RAF family kinases and EGFR, with an acceptable risk-benefit profile and antitumor activity in patients with
Identifiants
pubmed: 32182156
doi: 10.1200/JCO.19.02654
pmc: PMC7325368
doi:
Substances chimiques
BGB-283
0
Benzimidazoles
0
Naphthyridines
0
Protein Kinase Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT02610361']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2140-2150Références
Cell Physiol Biochem. 2017;43(6):2264-2276
pubmed: 29073606
J Pathol. 2012 Feb;226(3):413-20
pubmed: 22102435
J Am Acad Dermatol. 2015 May;72(5):809-15.e1
pubmed: 25748298
Obstet Gynecol Int. 2010;2010:984013
pubmed: 20396392
Nature. 2019 Nov;575(7781):217-223
pubmed: 31666701
J Clin Oncol. 2011 Apr 1;29(10):1239-46
pubmed: 21343559
Cancer Discov. 2020 Jan;10(1):54-71
pubmed: 31658955
Cancer Cell. 2014 Mar 17;25(3):272-81
pubmed: 24651010
J Natl Cancer Inst. 2003 Mar 19;95(6):484-6
pubmed: 12644542
Nat Commun. 2012 Mar 06;3:724
pubmed: 22395615
Cancer Discov. 2013 Feb;3(2):158-67
pubmed: 23242808
J Clin Oncol. 2012 May 10;30(14):1628-34
pubmed: 22454415
Eur J Cancer. 1999 Dec;35(13):1773-82
pubmed: 10673991
Mol Cancer Ther. 2007 Aug;6(8):2220-9
pubmed: 17699719
Prostaglandins Med. 1981 Mar;6(3):269-81
pubmed: 6894333
Am J Pathol. 2010 Oct;177(4):1611-7
pubmed: 20802181
Expert Opin Ther Targets. 2012 Jan;16(1):103-19
pubmed: 22239440
Int J Mol Sci. 2015 Sep 23;16(9):22976-88
pubmed: 26404261
Cancer Treat Rev. 2017 Nov;60:109-119
pubmed: 28946014
Clin Cancer Res. 2014 Apr 1;20(7):1965-77
pubmed: 24463458
Mol Cancer Ther. 2015 Oct;14(10):2187-97
pubmed: 26208524
Nature. 2011 Nov 23;480(7377):387-90
pubmed: 22113612
Br J Dermatol. 2017 Oct;177(4):914-923
pubmed: 28129674
N Engl J Med. 2011 Jun 30;364(26):2507-16
pubmed: 21639808
Br J Cancer. 2018 Jan;118(1):3-8
pubmed: 29235562
Ann Oncol. 2017 Oct 1;28(10):2581-2587
pubmed: 28961848
Hum Pathol. 2013 Mar;44(3):329-35
pubmed: 23089489
Cancer Discov. 2012 Mar;2(3):227-35
pubmed: 22448344
Life Sci. 1981 Apr 6;28(14):1641-6
pubmed: 6264257
Semin Nephrol. 2010 Nov;30(6):591-601
pubmed: 21146124
Lancet. 2012 Jul 28;380(9839):358-65
pubmed: 22735384
Clin Cancer Res. 2013 Feb 1;19(3):657-67
pubmed: 23251002