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Motzer RJ , Rini BI , McDermott DF , Redman BG , Kuzel TM , Harrison MR , Vaishampayan UN , Drabkin HA , George S , Logan TF , Margolin KA , Plimack ER , Lambert AM , Waxman IM , Hammers HJ
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial
J Clin Oncol. 2015 May 1;33(13) :1430-7
PMID: 25452452    PMCID: PMC4806782   
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PURPOSE: Nivolumab is a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. CONCLUSION: Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting.
1527-7755 Motzer, Robert J Rini, Brian I McDermott, David F Redman, Bruce G Kuzel, Timothy M Harrison, Michael R Vaishampayan, Ulka N Drabkin, Harry A George, Saby Logan, Theodore F Margolin, Kim A Plimack, Elizabeth R Lambert, Alexandre M Waxman, Ian M Hammers, Hans J P30 CA014236/CA/NCI NIH HHS/United States P30 CA022453/CA/NCI NIH HHS/United States Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States J Clin Oncol. 2015 May 1;33(13):1430-7. doi: 10.1200/JCO.2014.59.0703. Epub 2014 Dec 1.