Randomized phase II study of capecitabine with or without ramucirumab (IMC-1121B) or IMC-18F1 in patients with unresectable, locally advanced or metastatic breast cancer (mBC) previously treated with anthracycline and taxane therapy (CP20-0903/NCT01234402).

Abstract

TPS151 Background: Ramucirumab is a fully human IgG1 monoclonal antibody (MAb) that targets the VEGFR‐2, blocks the interaction of VEGF and VEGFR‐2 and neutralizes VEGF-induced mitogenesis of human endothelial cells. Treatment with DC101 (MAb targeting murine VEGFR-2) impairs vascular function and increases tumor hypoxia in the MDA-MB-231 breast cancer xenograft model (Cancer Res. 2006;66:3639-48) and inhibits tumor growth in cytotoxic therapy-resistant breast cancer xenograft models (Clin Cancer Research. 2002;8:221–32). IMC-18F1 is a fully human IgG1 MAb which targets human VEGFR-1 (Flt-1). IMC‐18F1 binds to VEGFR-1 and blocks receptor binding of VEGF-A, VEGF-B, and PlGF, and inhibits subsequent signaling. IMC-18F1 and MF1 (MAb targeting murine VEGFR-1) treatment with 5-FU/LV, cyclophosphamide, or doxorubicin resulted in enhanced antitumor efficacy compared with cytotoxic monotherapy in MD-MBA-231 tumor xenografts (Clin Cancer Res.2006;12:6573-84). Methods: This 3-arm study opened for accrual in 11/2010. Enrollment of 150 patients (pts) with unresectable, locally advanced or mBC, previously treated with anthracycline and taxane therapy, will occur at 30 US centers. The primary objective is PFS. Secondary objectives include tumor response, safety, PK, and immunogenicity. Association between clinical outcome and genetic polymorphisms, levels of plasma angiogenic proteins, and levels of VEGFR-1 positive circulating tumor cells and hematopoietic precursor cells will be assessed. Pts will be randomized in a 1:1:1 ratio to 1 of 3 arms in 21-day cycles as follows: capecitabine (1000 mg/m2 po BID for 14 days) plus ramucirumab (10 mg/kg) on Day 1 (Arm A); capecitabine plus IMC-18F1 (12 mg/kg) on Day 1 and Day 8 (Arm B); or capecitabine (Arm C). Pts in Arm C will be eligible to receive either MAb with capecitabine, after disease progression on capecitabine. Randomization will be stratified by triple-negative receptor status and prior antiangiogenic therapy. Pts will be treated until disease progression or other withdrawal criteria are met.