AMG 386 in combination with sorafenib in patients (pts) with metastatic renal cell cancer (mRCC): A randomized, double-blind, placebo-controlled, phase II study.

309 Background: AMG 386 inhibits angiogenesis by sequestering angiopoietin-1 and -2, thus preventing their interaction with the Tie2 receptor on endothelial cells. Combination with VEGF receptor inhibition has demonstrated additive effects in vivo. The efficacy and tolerability of sorafenib plus AMG 386, an investigational peptide-Fc fusion protein, were evaluated in mRCC pts. Methods: Treatment-naive pts with clear cell mRCC were randomized 1:1:1 to sorafenib 400 mgPO BID plus AMG 386 10 mg/kg (Arm A) or 3 mg/kg (Arm B) QW; or placebo (Arm C) IV QW. Endpoints were progression-free survival (PFS; primary); and (secondary) objective response rate (ORR), change in tumor burden, adverse events (AEs) and pharmacokinetics. Tumor assessment was performed at baseline and every 8 weeks thereafter. Results: 152 pts were randomized: Arms A/B/C, n=50/51/51. 60/61/61% of pts had intermediate and 40/39/37% had low MSKCC risk at baseline. PFS was similar in all 3 arms, whereas ORR was higher in the AMG 386 arms (Table)...