Development of biologic based therapies for rhabdomyosarcoma

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

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 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. In FY2022, the trial was prematurely closed due to a decision by our industry partner to discontinue stability testing and restrict our access to the investigational product ganitumab. At that time, we had accrued 13 patients onto the phase 1 part of this study which was complete, and had begin accrual onto the phase 2 part of this trial. This trial had 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, which were completed in FY2023. We have recently published the findings.