In FY2018, 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. Currently, we are enrolling patients into the highest dose level of ganitumab and dasatinib for the phase I portion of the trial. This trial has several aims including identification of the highest safe dose for this combination, evaluation of efficacy of this combination in patients with relapsed and refractory rhabdomyosarcoma, and correlative biologic studies of response and resistance, which are ongoing.
| Heske, Christine M; Yeung, Choh; Mendoza, Arnulfo et al. (2016) The Role of PDGFR-? Activation in Acquired Resistance to IGF-1R Blockade in Preclinical Models of Rhabdomyosarcoma. Transl Oncol 9:540-547 |
