title: Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.affiliation: 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.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: 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.
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.affiliation: 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.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.affiliation: 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.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.affiliation: 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.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.affiliation: 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.
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishampayan
authors.affiliation: 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.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Drabkin
authors.affiliation: 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.
authors.forename: Saby
authors.initials: S
authors.lastname: George
authors.affiliation: 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.
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Logan
authors.affiliation: 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.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.affiliation: 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.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Plimack
authors.affiliation: 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.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Lambert
authors.affiliation: 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.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Waxman
authors.affiliation: 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.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hammers
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D002170:Canada; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005387:Finland; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D000077594:Nivolumab