Robert J Motzer1, Brian I Rini2, David F McDermott2, Bruce G Redman2, Timothy M Kuzel2, Michael R Harrison2, Ulka N Vaishampayan2, Harry A Drabkin2, Saby George2, Theodore F Logan2, Kim A Margolin2, Elizabeth R Plimack2, Alexandre M Lambert2, Ian M Waxman2, Hans J Hammers2. 1. Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York; Saby George, Roswell Park Cancer Institute, Buffalo, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; David F. McDermott, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA; Bruce G. Redman, University of Michigan Comprehensive Cancer Center, Ann Arbor; Ulka N. Vaishampayan, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Timothy M. Kuzel, Northwestern University Feinberg School of Medicine, Chicago, IL; Michael R. Harrison, Duke University Medical Center, Durham, NC; Harry A. Drabkin, Medical University of South Carolina, Charleston, SC; Theodore F. Logan, Indiana University Simon Cancer Center, Indianapolis, IN; Kim A. Margolin, Stanford University, Stanford, CA; Elizabeth R. Plimack, Fox Chase Cancer Center, Philadelphia, PA; Alexandre M. Lambert, Bristol-Myers Squibb, Braine-l'Alleud, Belgium; Ian M. Waxman, Bristol-Myers Squibb, Princeton, NJ; and Hans J. Hammers, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. motzerr@mskcc.org. 2. Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York; Saby George, Roswell Park Cancer Institute, Buffalo, NY; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; David F. McDermott, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA; Bruce G. Redman, University of Michigan Comprehensive Cancer Center, Ann Arbor; Ulka N. Vaishampayan, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Timothy M. Kuzel, Northwestern University Feinberg School of Medicine, Chicago, IL; Michael R. Harrison, Duke University Medical Center, Durham, NC; Harry A. Drabkin, Medical University of South Carolina, Charleston, SC; Theodore F. Logan, Indiana University Simon Cancer Center, Indianapolis, IN; Kim A. Margolin, Stanford University, Stanford, CA; Elizabeth R. Plimack, Fox Chase Cancer Center, Philadelphia, PA; Alexandre M. Lambert, Bristol-Myers Squibb, Braine-l'Alleud, Belgium; Ian M. Waxman, Bristol-Myers Squibb, Princeton, NJ; and Hans J. Hammers, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Abstract
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.
RCT Entities:
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.
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