PURPOSE: To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of 
rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor 
(HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients 
with castration-resistant prostate cancer (CRPC).
EXPERIMENTAL DESIGN: This double-blinded phase II study randomized (1:1:1) 
patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. 
day 1, 5 mg twice a day orally days 1-21, respectively) plus 15 mg/kg 
rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The 
primary endpoint was overall survival (OS).
RESULTS: One hundred and forty-four patients were randomized. Median OS was 12.2 
versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in the 
combined rilotumumab versus control arms. Median progression-free survival was 
3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well 
tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. 
A trend toward unfavorable OS was observed in patients with high tumor MET 
expression regardless of treatment. Soluble MET levels increased in all 
treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab 
showed linear pharmacokinetics when co-administered with MP.
CONCLUSIONS: Rilotumumab plus MP had manageable toxicities and showed no 
efficacy improvements in this estimation study. High tumor MET expression may 
identify patients with CRPC with poorer prognosis.