Data from Phase I trial of ganitumab plus dasatinib to cotarget the insulin-like growth factor 1 receptor and Src family kinase YES in rhabdomyosarcoma

• DOI: 10.1158/1078-0432.c.6747873.v3
• Publication Date: 2024-09-16T12:33:25Z
• Authors: Srivandana Akshin...; R. Taylor. Sundby; Donna Bernstein; John W. Glod; Rosandra N. Kaplan; Marielle E. Yohe; Andrea M. Gross; Joanne Derdak; Haiyan Lei; Alexander Pan; Eva Dombi; Isabel Palacio-Yance; Kailey R. Herrera; Markku M. Miettinen; Helen X. Chen; Seth M. Steinberg; Lee J. Helman; Leo Mascarenhas; Brigitte C. Widemann; Fariba Navid; Jack F. Shern; Christine M. Heske
• Keywords: Src family kinase

<div>Abstract<p>Purpose: Antibodies against IGF-1R have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been to mediate antibody acquired resistance, and cotargeting resulted sustained murine RMS models. We conducted a phase I trial of the anti-IGF-1R ganitumab combined dasatinib, multi-kinase inhibitor targeting YES, (NCT03041701). Patients Methods: relapsed/refractory alveolar or embryonal measurable disease were eligible. All received 18 mg/kg intravenously every 2 weeks. Dasatinib dose was 60 mg/m2/dose (max 100 mg) oral once daily [dose level (DL)1] 70 twice (DL2). A 3+3 escalation design used, maximum tolerated (MTD) determined based on cycle 1 dose-limiting toxicities (DLTs). Results: Thirteen eligible patients, median age years (range 8-29) enrolled. Median number prior systemic therapies 3; all had radiation. Of 11 toxicity-evaluable 1/6 DLT at DL1 (diarrhea) 2/5 DL2 (pneumonitis, hematuria) confirming as MTD. nine response-evaluable one confirmed partial response (PR) for four cycles, stable (SD) six cycles. Genomic studies from cell-free DNA correlated response. Conclusions: combination dasatinib two weeks safe tolerable. This control rate 22% five months.</p></div>