Development of biologic based therapies for rhabdomyosarcoma

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

In FY2021, our phase I/II clinical trial testing the combination of the IGF-1R antibody ganitumab with dasatinib, a multi-kinase inhibitor targeting the SRC-family kinase YES in patients with relapsed and refractory rhabdomyosarcoma continued to accrue patients. This study was developed based upon preclinical work in our lab that identified YES activation as a bypass pathway for resistance to IGF-1R inhibition. Dual blockade of YES and IGF-1R demonstrated enhanced tumor cell growth inhibition in a number of preclinical models of both embryonal and alveolar rhabdomyosarcoma. We accrued 13 patients onto the phase 1 part of this study which is now complete. We are in the process of preparing the manuscript describing the findings. We accrued 1 additional patient onto the phase 2 part of this trial but due to a decision by our industry partner to discontinue stability testing and restrict our access to the investigational product ganitumab, we were forced to close to accrual in late 2021. This trial has several aims including identification of the highest safe dose for this combination (complete), evaluation of efficacy of this combination in patients with relapsed and refractory rhabdomyosarcoma (incomplete), and correlative biologic studies of response and resistance (currently ongoing).