Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Phe1245Cys (p.F1245C) ( ENST00000389048.8, ENST00000618119.4, ENST00000642122.1 )
ALK p.Phe1245Cys (p.F1245C) ( ENST00000389048.8, ENST00000618119.4, ENST00000642122.1 )
Associated Disease
neuroblastoma
Source Database
CIViC Evidence
Description
Patient derived xenografts of neuroblastoma Felix cells with F1245C ALK mutation in CB17 SCID mice showed growth inhibition with crizotinib treatment over control, and mice had improved duration of event-free survival (EFS) with crizotinib treatment over vehicle, but EFS with crizotinib went down to 0% by six weeks. In contrast, PF-06463922 treatment induced complete tumor regression and EFS rate of 100% at six weeks. PF-06463922 inhibited viability in Felix cells at 37x efficacy over crizotinib, with IC50 values of 21.8 +/- 0.4 and 814.0 +/- 119 respectively. PF-06463922 was well tolerated in the animal models.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1330
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/549
Rating
3
Evidence Type
Predictive
Disease
Neuroblastoma
Evidence Direction
Supports
Drug
Lorlatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
26554404
Drugs
Drug NameSensitivitySupported
LorlatinibSensitivitytrue