Safety and efficacy of AMG 386 in combination with sunitinib in patients with metastatic renal cell carcinoma (mRCC) in an open-label multicenter phase II study.

4606 Background: AMG 386, an investigational peptide-Fc fusion protein, inhibits angiogenesis by disrupting the angiopoietin/Tie2 axis. We evaluated the safety and efficacy of AMG 386 plus sunitinib in patients (pts) with mRCC. Methods: Adults with mRCC who were naive to angiogenesis inhibitors were sequentially enrolled to 2 cohorts: sunitinib 50 mg PO QD (4 wks on, 2 wks off) plus AMG 386 at 10 mg/kg (A) or 15 mg/kg (B) IV QW. Primary endpoints: adverse events (AEs), dose interruptions/reductions due to AEs in the first 12 wks of treatment; secondary endpoints included: progression-free survival (PFS) and response rate (ORR). Results: 85 pts received ≥1 dose of study medication (A/B, n=43/42). In A/B, 88%/76% were male and 30%/36% were age ≥65; MSKCC risk scores were low (40%/36%) or intermediate (60%/62%). For A/B: median follow-up time was 19.6/12.0 mos; AMG 386 discontinuations due to AEs were 16%/29%; and grade ≥3 treatment-related AEs occurred in 72%/74% with virtually all attributed to sunitinib. ...