Bevacizumab (Bev) alone or in combination with TRC105 for metastatic renal cell cancer (mRCC): A California Cancer Consortium clinical trial.

4542 Background: Inhibition of vascular endothelial growth factor (VEGF) pathway is effective in mRCC, but resistance inevitably develops. CD105 (endoglin) is highly expressed on endothelial cells and has been shown in preclinical models to mediate resistance to VEGF pathway inhibitors, in part due to TGF-beta signaling. TRC105 is a monoclonal antibody against CD105 which has been shown to be tolerable in combination with Bev at full doses. Methods: Eligible mRCC patients (pts) with any histologic subtype may have received 1-4 prior systemic therapies including cytokines, VEGF, or mTOR agents. Bev was administered at 10 mg/kg IV on day 1 and 15 of 28-day cycles as a single agent (Arm A) or with TRC105 10 mg/kg IV on days 1, 8, 15, and 22 (Arm B). Primary endpoint was progression-free survival (PFS). A total of 88 pts were to be randomized to detect a halving of PFS with 80% power and α = 0.1. An interim analysis for futility was conducted after 44 pts had PFS evaluated. Results: Enrollment was halted afte...