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Ref Type Journal Article
PMID (21298745)
Authors Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C, Smith MA, Houghton PJ
Title Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program.
Journal Pediatric blood & cancer
Vol 56
Issue 4
Date 2011 Apr
URL
Abstract Text BMS-754807 is a small molecule ATP-competitive inhibitor of the type-1 insulin-like growth factor receptor currently in phase 1 clinical trials.BMS-754807 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro panel at concentrations ranging from 1.0 nM to 10 µM and was tested against the PPTP in vivo panels at a dose of 25 mg/kg administered orally BID for 6 days, repeated for 6 weeks.In vitro BMS-754807 showed a median EC(50) value of 0.62 µM against the PPTP cell lines. The median EC(50) for the four Ewing sarcoma cell lines was less than that for the remaining PPTP cell lines (0.19 µM vs. 0.78 µM, P = 0.0470). In vivo BMS-754807 induced significant differences in EFS distribution compared to controls in 18 of 32 evaluable solid tumor xenografts (56%) tested, but in none of the ALL xenografts studied. Criteria for intermediate activity for the time to event activity measure (EFS T/C > 2) were met in 7 of 27 solid tumor xenografts evaluable for this measure. The best response was PD2 (progressive disease with growth delay), which was observed in 18 of 32 solid tumor xenografts. PD2 responses were most commonly observed in the rhabdomyosarcoma, neuroblastoma, osteosarcoma, Ewing sarcoma, and Wilms tumor panels.BMS-754807 activity in vitro is consistent with a specific IGF-1R effect that has half-maximal response in the 0.1 µM range and that is observed in a minority of the PPTP cell lines. In vivo intermediate activity was most commonly observed in the neuroblastoma and rhabdomyosarcoma panels.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown acute lymphoblastic leukemia no benefit BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in no change in event-free survival in 100% (7/7) of cell ine xenograft models of acute lymphocytic leukemia (PMID: 21298745). 21298745
Unknown unknown rhabdomyosarcoma not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 33% (2/6) of cell line xenograft models of rhabdomyosarcoma (PMID: 21298745). 21298745
Unknown unknown Ewing sarcoma not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 50% (2/4) of cell line xenograft models of Ewing sarcoma (PMID: 21298745). 21298745
Unknown unknown rhabdoid cancer not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 100% (3/3) of cell line xenograft models of rhabdoid tumor (PMID: 21298745). 21298745
Unknown unknown osteosarcoma not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 67% (4/6) of cell line xenograft models of osteosarcoma (PMID: 21298745). 21298745
Unknown unknown renal Wilms' tumor not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 100% (3/3) of cell line xenograft models of Wilms tumor (PMID: 21298745). 21298745
Unknown unknown neuroblastoma not applicable BMS-754807 Preclinical - Cell line xenograft Actionable In a preclinical study, BMS-754807 treatment resulted in significant tumor growth delay in 67% (4/6) of cell line xenograft models of neuroblastoma (PMID: 21298745). 21298745