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AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney †
A randomized, double-blind, placebo-controlled, phase 2 study
Article first published online: 12 JUN 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 24, pages 6152–6161, 15 December 2012
How to Cite
Rini, B., Szczylik, C., Tannir, N. M., Koralewski, P., Tomczak, P., Deptala, A., Dirix, L. Y., Fishman, M., Ramlau, R., Ravaud, A., Rogowski, W., Kracht, K., Sun, Y.-N., Bass, M. B., Puhlmann, M. and Escudier, B. (2012), AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney . Cancer, 118: 6152–6161. doi: 10.1002/cncr.27632
This study is registered at ClinicalTrials.gov, identifier NCT00467025.
- Issue published online: 3 DEC 2012
- Article first published online: 12 JUN 2012
- Manuscript Accepted: 12 APR 2012
- Manuscript Received: 15 FEB 2012
- AMG 386;
- clear cell renal cell carcinoma;
- randomized controlled trial;
- phase 2 clinical trial
This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study.
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-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS).
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], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar 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.
In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib. Cancer 2012. © 2012 American Cancer Society.