Activity of R1507, a monoclonal antibody to the insulin-like growth factor-1 receptor (IGF1R), in patients (pts) with recurrent or refractory Ewing's sarcoma family of tumors (ESFT): Results of a phase II SARC study.

Abstract

10000 Background: IGF has been implicated in sarcoma development. Cell line and nude mouse experiments of antibody mediated inhibition of IGF1R demonstrated significant activity in single agent and in combination chemotherapy studies. Antibody mediated inhibition of IGF1R induced clinical responses in ESFT pts in several phase I studies. R1507 monotherapy was explored in this phase II single arm trial. Methods: Eligibility included recurrent/refractory, measurable disease, age ≥ 2 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered IV at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks × 4 and every 12 wks thereafter. Results: From 12/07-8/09, 125 patients with ESFT from 31 sarcoma centers in the US, Europe, and Australia were treated. Age ranged from 3-78 yrs (median=25 yrs) and 83 (66%) were male. 18 pts had CR or PR (14.4%). 12 pts responded at least 6 weeks with a median duration of 25 weeks. Median survival was 7.6 months. Gr 3-4 toxicities occurred in 16 pts including: diarrhea (2), anemia (2), thrombocytopenia (2), and neutropenia (2). Importantly, there were no gr 3-4 hyperglycemic or cardiacevents reported. Many investigators noted the need for weekly IV administration was a significant burden to pts and caregivers. Conclusions: R1507 is active as monotherapy in pts with metastatic ESFT. A major task moving forward with IGFIR Ab therapy in ESFT will be to identify predictors of response so that pt enrichment strategies can be undertaken. Studies combining this new drug with other effective therapies earlier in the treatment of disease are predicted to have significant clinical impact. Finally, studies are needed to address mechanisms of resistance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche