Safety, pharmacokinetics and preliminary activity of the anti-IGF-IR antibody CP-751,871 in patients with sarcoma

Abstract

10501 Background: CP-751,871 is a fully human IgG2 monoclonal antibody against the insulin-like growth factor-I receptor (IGF-IR). Inhibition of the IGF-IR is a promising novel therapy for sarcoma. IGF-IR is implicated in autocrine and paracrine control of sarcoma, and IGF-IR blockade increases apoptosis and decreases migration, invasion, metastatic spread, and angiogenesis in sarcoma models. Methods: A cohort of patients (pts) ≥9 years of age with relapsed or refractory sarcoma, ECOG PS 0/1, and adequate hematological and biochemical function was opened with the primary objective of investigating the safety and tolerability of CP-751,871 in this pt population. Secondary objectives included evaluating pharmacokinetics and preliminary efficacy (RECIST). CP-751,871 was given by intravenous infusion at a dose of 20 mg/kg either q28 or q21 days. Results: Twenty-two pts were enrolled. Sarcoma subtypes treated were Ewing’s (n=9), synovial (n=5), desmoplastic small round cell tumors (DSRCT; n=3), rhabdomyosarcoma (n=2), fibrosarcoma (n=2), and chondrosarcoma (n=1). Median pt age was 35 years (range 12–63); 64% had ECOG PS 1. Median number of previous regimens was 3 (range 1–5). Pts received a median of 2 treatment cycles (range 1–16). Grade ≥3 treatment-related adverse events (CTCAE v3.0) reported included grade 4 uric acid increase (1 pt) and grade 3 bilateral deep-vein thrombosis (1 pt). Pharmacokinetics of CP-751,871 in sarcoma pts were comparable to those in other pt populations, with a half-life supporting the q21 or q28 day dosing regimen. Among 19 pts evaluable for response, one partial response was observed in a 12-year-old pt with Ewing’s sarcoma. Disease stabilization >3 months was observed in 6 pts (1 fibrosarcoma, 1 chondrosarcoma, 1 DSRCT, 1 synovial and 2 Ewing’s sarcoma pts). Six pts remain on study. Conclusions: CP-751,871 was well tolerated in pts with relapsed and/or refractory sarcoma. Preliminary activity in Ewing’s sarcoma warrants further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology ImClone Systems Incorporated, Pfizer Oncology, sanofi-aventis Pfizer Oncology ImClone Systems Incorporated, sanofi-aventis Novartis, Pfizer Oncology, sanofi-aventis