(ChemotherapyAdvisor) – The fully human monoclonal antibody against type-1 insulin-like growth factor receptor (IGF1R), ganitumab, is well tolerated and demonstrated antitumor activity in patients with advanced recurrent metastatic Ewing family tumors (EFT) or desmoplastic small round cell tumors (DSRCT), results of a Phase 2 open-label study in the Journal of Clinical Oncology online April 16 have found.
The investigators enrolled 38 patients, 22 with EFT and 16 with DSRCT, and administered ganitumab 12mg/kg every two weeks for one or more doses. Of 35 patients assessed for response, the objective response rate was 6% (2 partial responses); 49% (17 patients) had stable disease, including 4 patients who had stable disease for ≥24 weeks, contributing to a clinical benefit rate of 17%.
Ganitumab-related adverse events (AEs) were experienced by 24 patients (63%). Grade 3-related AEs included hyperglycemia (n=2), thrombocytopenia (n=5), neutropenia (n=2), leukopenia (n=1), and transient ischemic attack (n=1). No grade 4 or 5 treatment-related AEs were observed.
Analysis of EWS-Fli1 translocations by RNA sequencing and fluorescent in situ hybridization revealed novel translocations in EFT and DSCRT. Although elevated IGF-1 levels were observed postdose, they observed no apparent relationship between tumor response and IGF-1 levels or EWS gene translocations.
“Further studies are required to identify the subset of patients most likely to benefit from anti-IGF1R therapy, determine the role of the IGF1R pathway in the pathogenesis and propagation of EFT and DSRCT, and evaluate potential enhanced or additive effects of IGF1R inhibition by combining IGF1R inhibitors with other targeted inhibitors or with chemotherapy,” they concluded.