1051PD - Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): biomarker-based results from a r...

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Renal Cell Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Toni Choueiri
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors T. Choueiri1, M.N. Fishman2, B. Escudier3, J.J. Kim4, H. Kluger5, W.M. Stadler6, J.L. Perez-Garcia7, D. McNeel8, B. Curti9, M.R. Harrison10, E.R. Plimack11, L. Appleman12, L. Fong13, C. Drake14, L. Cohen15, S. Srivastava15, M. Jure-Kunkel15, Q. Hong16, J. Kurland17, M. Sznol18
  • 1Division Of Solid Tumor Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Genitourinary Program, H. Lee Moffitt Cancer CenterUniversity of South Florida, US-33612 - Tampa/US
  • 3Medical Oncology, Gustave-Roussy, 94805 - Villejuif/FR
  • 4Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 21202 - Baltimore/US
  • 5Yale Cancer Center, Yale Comprehensive Cancer Center (Smilow Cancer Hospital at Yale-New Haven), 06519 - New Haven/US
  • 6Medical Oncology, University of Chicago, Chicago/US
  • 7Campus Universitario S/n, University of Navarra, Barcelona/ES
  • 8Departement Of Medicine, University of Wisconsin, Madison/US
  • 9Director Of Genitourinary Oncology Research, Providence Cancer Center, Portland/US
  • 10Department Of Medicine, Duke University Medical Center, Durham/US
  • 11Department Of Medicine, Fox Chase Cancer Center, Philadelphia/US
  • 12Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh/US
  • 13Helen Diller Family-comprehensive, University of California San Franscisco Medical Center, San Franscisco/US
  • 14Helen Diller Family-comprehensvie, University of California San Franscisco Medical Center, San Francisco/US
  • 15Department Of Oncology, Bristol Myers-Squibb, Princeton/US
  • 16Oncology, Bristol Myers-Squibb, Princeton/US
  • 17Bio Research, Bristol-Myers Squibb, Princeton/US
  • 18Section Of Medicine Oncology, Yale Cancer Center, New Haven/US




Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has shown encouraging activity in mRCC. This trial assessed immunomodulatory activity, antitumor response, and safety of nivolumab in patients (pts) with mRCC.


91 pts received nivolumab IV Q3W: previously treated pts (1-3 prior therapies; ≥1 anti-angiogenic agent) received 0.3 (n = 22), 2 (n = 22), or 10 mg/kg (n = 23); untreated pts received 10 mg/kg (n = 24). Fresh biopsies and serum were obtained at baseline (BL) and at nivolumab cycle 2 day 8 (C2D8; biopsy) and cycle 4 day 1 (C4D1; serum). The primary objective assessed immunomodulatory activity of nivolumab on serum chemokines (CXCL9, CXCL10) and tumor T cell infiltrates from BL to posttreatment. Secondary/exploratory objectives included safety, antitumor activity (ORR, RECIST 1.1; PFS), BL and treatment-induced changes in PD-1 ligand (PD-L1) expression (Dako immunohistochemistry assay; PD-L1 positivity: >5% tumor membrane staining at any intensity) and association of clinical activity with BL PD-L1 expression.


T cell infiltrates increased by a median of 70% (CD3 + ; range 53-220%) and 88% (CD8 + ; 61-257%) from BL to C2D8. Mean increase from BL to C4D1 was 180% for CXCL9 and 79% for CXCL10. In evaluable pts ORR was 17% (15/90); 18% previously treated, 13% untreated pts. Median duration of response was 64 weeks; 6 (43%) responses are ongoing. PFS rate at 48 wks was 18% (16/90). Grade 3-4 AEs occurred in 15% (14/91): colitis and elevated AST (n = 2 each), diarrhea, elevated ALT and pneumonitis (n = 1 each). Of 56 evaluable pretreatment biopsies, 18 (32%) were PD-L1+. ORR was 22% (4/18) for PD-L1+ pts vs 8% (3/38) for PD-L1–. In 5/27 (19%) matched biopsy pairs PD-L1 expression increased >5% by C2D8.


In this prospective study, changes in biomarkers were consistent with PD-1 inhibition, evidence of nivolumab's immunomodulatory effects in serum and the tumor microenvironment. Nivolumab demonstrated antitumor activity and manageable safety in pts with previously treated or untreated mRCC. Responses were numerically higher in PD-L1+ pts, but also present in PD-L1– pts.


T. Choueiri: Ad Board: Pfizer, Novartis, GSK, Bayer, Aveo Research: Pfizer; M.N. Fishman: I have received funding for research trials from Bristol Myers Squibb; B. Escudier: I have received compensation for consultation/ advisory position to the following: Bayer, Pfizer, Novartis I have received honoraria from the following: Bayer, Roche, Pfizer, Genentech, Novartis, AVEO, GSK; W.M. Stadler: University of Chicago/I has received funding for research from Bristol Myers-Squibb; J.L. Perez-Garcia: 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; I have received honoraria from: Novartis, Prometheus; I have received funding for research from: BMS, Argos, Exelixis, Pfizer, Exelixis; E.R. Plimack: Has received grants and/or personal fees from: BMS, GSK, Dendreon, Astellas, Pfizer, Amgen, Acceleron, MedImmune, Merck, Lilly, AZ; L. Appleman: I have received funding from Bristol Myers-Squibb; L. Fong: I have received funding for research from Bristol Myers-Squibb; C.G. Drake: Sponsored Research: Aduro Biotech, BMS, Janssen, I have consulted to: BMS, Compugen, Dendreon, Pfizer, Roche/ Genentech, NexImmune; L. Cohen: I am an employee of Bristol Myers Squibb; S. Srivastava: I am an employee of Bristol Myers Squibb; M. Jure-Kunkel: I am an employee of and have stock or other ownership interest in BMS; Q. Hong: I am an employee of and have stock or other ownership interest in BMS; J. Kurland: I am an employee of and have stock or other ownership interest in BMS; M. Sznol: I have received personal Fees from BMS, Amgen, Medimmune, Genentech, Symphogen, Nektar, Anaeropharma, Immune Design, Merus, Lion Biotechnologies, Kyowa-Kirin, Astra-Zeneca-Medimmune. All other authors have declared no conflicts of interest.