A Multicenter, Randomized Phase Ii Study Of Rilotumumab (R) (Amg 102) Or Placebo (Pbo) Plus Mitoxantrone (M) And Prednisone (P) In Patients (Pts) With Previously Treated Castrate-Resistant Prostate Cancer (Crpc).

115 Background: R is an investigational, fully human monoclonal antibody to hepatocyte growth factor (HGF) that prevents HGF binding to the c-Met receptor. We conducted a 3-arm, double-blind, randomized phase 2 study to examine the safety and estimate the efficacy of adding R to MP in CRPC pts.Eligible pts (≥ 18 years) had progressive CRPC, prior taxane-based chemotherapy, and ECOG PS ≤ 1. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), PSA response, pharmacokinetics (PK), and safety. Pts were randomized 1:1:1 to R (15 mg/kg IV Q3W) + MP (12 mg/m(2) IV Q3W, 5 mg BID orally) [Arm A]; R (7.5 mg/kg IV Q3W) + MP [Arm B]; or Pbo + MP [Arm C] for up to 12 cycles.142 pts (Arms A/B/C: 45/48/49 pts) were enrolled between March 10, 2009 and December 2, 2009. Median age: 67/67/69 yrs; ECOG PS 1: 69/71/61%; progression during prior taxane therapy: 51/54/47%. Most common reason for discontinuation was disease progression (60/58/69%). Efficacy is shown in the table. R + MP showed no statistically significant difference in OS. Adverse events (AE) with ≥ 5% difference in Arms A + B vs C included peripheral edema, 24/8%; nausea, 44/35%; mucosal inflammation, 8/0%; rash, 8/0%; arthralgia, 16/8%; neutropenia, 16/8%. Grade 5 AE: cardiac arrest, pulmonary embolism, septic shock (1 each in Arm B). R showed linear PK with mean (SD) steady state Cmin of 251 (100) and 127 (35) μg/mL and Cmax of 609 (126) and 297 (75) μg/mL in Arms A and B. R did not affect PK of M.R + MP was well tolerated with no unexpected toxicities. R + MP showed no significant improvements in OS, PFS, and PSA response. [Table: see text].