810O - Randomized, dose-ranging phase II trial of nivolumab for metastatic renal cell carcinoma (mRCC)

Date 29 September 2014
Event ESMO 2014
Session Genitourinary tumours, non prostate immunotherapy
Topics Renal Cell Cancer
Presenter Robert Motzer
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors R.J. Motzer1, B.I. Rini2, D.F. McDermott3, B. Redman4, T. Kuzel5, M.R. Harrison6, U.N. Vaishampayan7, H. Drabkin8, S. George9, T. Logan10, K. Margolin11, E.R. Plimack12, I. Waxman13, A. Lambert14, H. Hammers15
  • 1Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Taussig Cancer Institute, Cleveland/US
  • 3Dana-farber/harvard Cancer Center, Beth Israel Deaconess Medical Center, Boston/US
  • 4Department Of Oncology, 4University of Michigan Comprehensive Cancer Center, Ann Arbor/US
  • 5Feinberg School Of Medicine, Northwestern University, Chicago/US
  • 6Medical Center, Duke University, Durham/US
  • 7Karmanos Cancer Center, Wayne State University, Detroit/US
  • 8Oncology, Medical University of South Carolina, Charleston/US
  • 9Oncology, Roswell Park Cancer Institute, Buffalo/US
  • 10Simon Cancer Center, Indiana University, Indianapolis/US
  • 11Medical Oncology, Seattle Cancer Care Alliance, Seattle/US
  • 12Oncology, Fox Chase Cancer Center, Philadelphia/US
  • 13Oncology, Bristol-Myers Squibb, Princeton/US
  • 14Biostatistics, Bristol-Myers Squibb, Braine-l’Alleud/BE
  • 15Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore/US



Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, has shown encouraging survival and manageable safety in pretreated mRCC patients (pts). This phase II trial (NCT01354431) assesses 3 nivolumab doses in mRCC pts pretreated with targeted VEGF pathway agents. We previously reported no dose response relationship with 3 doses of nivolumab (primary objective). Here we present updated overall survival (OS) and duration of response (DOR) data.


Pts with clear-cell mRCC (≥1 agent targeting VEGF pathway; ≤3 prior systemic therapies) were randomized (blinded 1:1:1) to IV nivolumab 0.3, 2, or 10 mg/kg every 3 weeks until progression or toxicity. The primary objective was to evaluate the dose response relationship measured by progression-free survival (PFS). Secondary objectives included OS, objective response rate (ORR), and safety.


All pts (N = 168) received prior systemic therapy (70% received ≥2) including VEGF receptor TKIs (98%), mTOR inhibitors (38%), and immunotherapy (24%). 25% were MSKCC poor risk. PFS and ORR were similar across doses (Table). The median DOR was not reached for 0.3 and 2 mg/kg, and was 22.3 months for 10 mg/kg (Table). Median OS was 18.2 months for 0.3 mg/kg and approximately 25 months for 2 and 10 mg/kg (Table). Across doses, 19/35 responders (54%) had objective responses lasting >12-20+ months. Rates of grade 3-4–related adverse events (AEs) were ≤17% for all doses (Table). There was no grade 3-4 pneumonitis. For 0.3, 2, and 10 mg/kg, 1 (2%), 6 (11%), and 4 (7%) pts, respectively, had treatment-related AEs that led to discontinuation.


In this phase II trial nivolumab was associated with encouraging efficacy, with no dose response relationship observed for PFS or ORR. Median OS range was 18.2-25.5 months; longer median OS was reported at 2 and 10 mg/kg. The safety profile of nivolumab was acceptable for all doses with no grade 3-4 pneumonitis observed.

0.3 mg/kg n = 60a 2 mg/kg n = 54 10 mg/kg n = 54
Median PFS, months (80% CI) 2.7 (1.9-3.0) 4.0 (2.8-4.2) 4.2 (2.8-5.5)
ORR, n (%) 12 (20) 12 (22) 11 (20)
Median DOR, months NR NR (4.2-NR) 22.3 (4.8-NR)
Median OS, months (80% CI) 18.2 (16.2-24.0) 25.5 (19.8-28.8) 24.7 (15.3-26.0)
Treatment-related AEs, n(%) 44 (75) 36 (67) 42 (78)
Grade 3-4 AEs, n (%) 3 (5) 9 (17) 7 (13)

aSafety analysis included 59 treated pts. CI, confidence interval; NR, not reached.


R.J. Motzer: I have: consulted for the following companies: Pfizer, Merck, Genentech received funding for research from the following companies: Bristol Myers Squibb, Pfizer, GSK, Novartis provided expert testimony for the following companies: Pfizer; B.I. Rini: I have consulted for the following companies: Pfizer, BMS, Merck, GSK; received funding for research from: Pfizer, BMS, Immatics, GSK, Roche, Acceleron; D.F. McDermott: I have received honoraria from and worked as a consultant/ in an advisory capacity to Bristol-Myers Squibb; T. Kuzel: I have received funding for research from Bristol Myers Squibb; M.R. Harrison: I have: • consulted/worked in advisory role to: Novartis, AVEO, Exelixis, Bayer • received honoraria from: Novartis, Prometheus • received funding for research from: BMS, Argos, Exelixis, Pfizer, Exelixis; S. George: I have consulted/worked in advisory role to: Bayer/ Algeta, Novartis, Sanofi and Astellas (Aveo/ Medivation). Received research funding from: GSK; T. Logan: consulted to and received research funding from: Argos,Aveo, BMS, Celgene, GSK, Novartis, Pfizer, Prometheus, Schering Plough, Wyeth research funding from: Entremed, Exelixis, Genetech, GSK, Inmatics, Lilly, MedImmune, Roche, Synta, Threshold; E.R. Plimack: Has received grants and/or personal fees from: BMS, GSK, Dendreon, Astellas, Pfizer, Amgen, Acceleron, MedImmune, Merck, Lilly, AZ; I. Waxman: I am an employee of Bristol Myers Squibb; A. Lambert: I am an employee of and have stock or other ownership interest in BMS; H. Hammers: Has received Honoraria from Ono Pharma USA. All other authors have declared no conflicts of interest.