{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:14:19Z","timestamp":1791216859813,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:00:00Z","timestamp":1339459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin\u20101 and angiopoietin\u20102 with Tie2 (tyrosine kinase with immunoglobulin\u2010like and EGF\u2010like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg\/kg (arm A) or 3 mg\/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open\u2010label AMG 386 at 10 mg\/kg qw plus sorafenib following disease progression. The primary endpoint was progression\u2010free survival (PFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60\u20101.30; <jats:italic>P<\/jats:italic> = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%\u201053%), 37% (24%\u201052%), and 25% (14%\u201040%). Among 30 patients in arm C who had disease progression and subsequently received open\u2010label AMG 386 at 10 mg\/kg qw, the objective response rate was 3% (95% CI, 0%\u201017%). Frequently occurring adverse events (AEs) included diarrhea (arms A\/B\/C, 70%\/67%\/56%), palmar\u2010plantar erythrodysesthesia syndrome (52%\/47%\/54%), alopecia (50%\/45%\/50%), and hypertension (42%\/49%\/46%). Fifteen patients had grade 4 AEs (arms A\/B\/C, n = 3\/7\/5); 4 had fatal AEs (n = 2\/1\/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib. Cancer 2012. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.27632","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T12:29:30Z","timestamp":1339504170000},"page":"6152-6161","source":"Crossref","is-referenced-by-count":95,"title":["AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney"],"prefix":"10.1002","volume":"118","author":[{"given":"Brian","family":"Rini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezary","family":"Szczylik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar 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