biostudies-literatureAkshintala SIntramural NIH HHSNational Cancer InstituteNCI NIH HHSUSC Norris Comprehensive Cancer Center3329-3339https://www.ebi.ac.uk/biostudies/studies/S-EPMC10529967biostudies-literatureUnknown29(17)<h4>Purpose</h4>Antibodies against insulin-like growth factor (IGF) type 1 receptor have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been shown to mediate IGF type 1 receptor (IGF-1R) antibody acquired resistance, and cotargeting IGF-1R and YES resulted in sustained responses in murine RMS models. We conducted a phase I trial of the anti-IGF-1R antibody ganitumab combined with dasatinib, a multi-kinase inhibitor targeting YES, in patients with RMS (NCT03041701).<h4>Patients and methods</h4>Patients with relapsed/refractory alveolar or embryonal RMS and measurable disease were eligible. All patients received ganitumab 18 mg/kg intravenously every 2 weeks. Dasatinib dose was 60 mg/m2/dose (max 100 mg) oral once daily [Clinical cancer research : an official journal of the American Association for Cancer ResearchPhase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma.PMC10529967P30 CA014089ZIA BC0117455P30CA014089-45Widemann BCHeske CMGross AMLei HBernstein DPalacio-Yance IMascarenhas LPan AMiettinen MMShern JFSteinberg SMKaplan RNHerrera KRDombi EHelman LJAkshintala SNavid FYohe MEChen HXSundby RTDerdak JGlod JWfalsePhase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma.<h4>Purpose</h4>Antibodies against insulin-like growth factor (IGF) type 1 receptor have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been shown to mediate IGF type 1 receptor (IGF-1R) antibody acquired resistance, and cotargeting IGF-1R and YES resulted in sustained responses in murine RMS models. We conducted a phase I trial of the anti-IGF-1R antibody ganitumab combined with dasatinib, a multi-kinase inhibitor targeting YES, in patients with RMS (NCT03041701).<h4>Patients and methods</h4>Patients with relapsed/refractory alveolar or embryonal RMS and measurable disease were eligible. All patients received ganitumab 18 mg/kg intravenously every 2 weeks. Dasatinib dose was 60 mg/m2/dose (max 100 mg) oral once daily [2023-01-01T00:00:00Z2023 Sep2026-04-29T14:09:23.181Z2025-04-20T03:01:35.024ZS-EPMC105299673739899210.1158/1078-0432.ccr-23-070910.1158/1078-0432.CCR-23-0709