1052PD - Nivolumab (N) (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib (S) or pazopanib (P) in patients (pts) with metastatic renal cell car...

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Anticancer Agents
Renal Cell Cancer
Biological Therapy
Presenter Asim Amin
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors A. Amin1, E.R. Plimack2, J.R. Infante3, M. Ernstoff4, B.I. Rini5, D.F. McDermott6, J. Knox7, S. Pal8, M. Voss9, P. Sharma10, C.K. Kollmannsberger11, D. Heng12, J. Spratlin13, Y. Shen14, J. Kurland15, P. Gagnier15, H. Hammers16
  • 1Medical Oncology, Levine Cancer Institute, 28204 - Charlotte/US
  • 2Department Of Oncology, Fox Chase Cancer Center, Philadelphia/US
  • 3Drug Development, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 4Geisel School Of Medicine, Dartmouth Hitchcock Medical Center, Lebanon/US
  • 5Taussig Cancer Institute, Cleveland Clinic, Cleveland/US
  • 6Dana-farber/harvard Cancer Center, Beth Israel Deaconess Medical Center, Boston/US
  • 7Princess Margaret Cancer Centre, University of Toronto, Toronto/CA
  • 8Department Of Oncology, City of Hope Comprehensive Cancer Center, Duarte/US
  • 9Department Of Oncology, Memorial Sloan Kettering Cancer Center, New York City/US
  • 10University Of Texas, MD Anderson Cancer Center, Houston/US
  • 11Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 12Tom Baker Cancer Center, University of Calgary, Calgary/CA
  • 13Oncology, Cross Cancer Institute, T6G1Z2 - Edmonton/CA
  • 14Biostatistics, Bristol-Myers Squibb, Princeton/US
  • 15Bio Research, Bristol-Myers Squibb, Princeton/US
  • 16Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 21231 - Baltimore/US




Antiangiogenic agents S and P are standard of care in mRCC, but effects are not durable. N, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has clinical activity in mRCC. VEGF TKIs have been shown to suppress Tregs and MDSCs making the immune environment more conducive for T cell-mediated antitumor activity. Combining VEGF TKIs with positive immune modulation may result in greater and more durable therapeutic benefit. We report preliminary results of a phase I trial of N in combination with S or P in mRCC.


mRCC pts received N in combination with S (50 mg, 4 wk on/2 wk off; arm S) or P (800 mg daily; arm P) until progression/unacceptable toxicity. Starting dose of N was 2 mg/kg IV every 3 wk (N2), with planned escalation to 5 mg/kg IV every 3 wk (N5). Based on tolerability, arm S N5 was expanded to treatment-naïve pts. Primary objectives were safety/tolerability and determination of maximum tolerated dose (MTD) for the combinations; secondary objective was antitumor activity.


7 pts each were treated on arms S N2 and N5. No dose-limiting toxicities (DLTs) were observed and MTD was not reached; thus N5 was expanded by 19 pts (total n = 33). Arm P had 20 pts at N2; 4 DLTs (elevated ALT/AST [n = 3], fatigue [n = 1]) were observed, leading to closure of the arm. Grade 3-4-related adverse events (AEs) were observed in 27/33 pts (82%) in arm S and 14/20 pts (70%) in arm P. Most common related grade 3-4 AEs were elevated ALT and hypertension (18% each), hyponatremia and lymphocyte count decreased (15% each) in arm S, and elevated ALT and AST, and diarrhea (20% each) and fatigue (15%) in arm P. Grade 3 pneumonitis occurred in 1 pt (arm S, N5). Grade 3-4-related AEs led to discontinuation in 10/33 pts (30%; 2 N2, 8 N5) in arm S and 4/20 pts (20%) in arm P. Objective response rate was 52% (17/33) in arm S and 45% (9/20) in arm P. Responses occurred by first assessment (6 wk) in 41% (arm S) and 56% (arm P) of pts. Duration of response (wk) was 18.1-80+ in arm S and 12.1-90.1+ in arm P. Progression-free survival rate at 24 wk was 79% for arm S and 55% for arm P.


N plus S showed encouraging antitumor activity and a manageable safety profile in pts with mRCC. Arm P was closed due to DLTs.


A. Amin: I have worked as a consultant/ in an advisory capacity to: Bristol Myers Squibb I have received Honoraria from: Bristol Myers Squibb; E.R. Plimack: I have received grants and/or personal fees from: BMS, GSK, Dendreon, Astellas, Pfizer, Amgen, Acceleron, MedImmune, Merck, Lilly, AZ; M. Ernstoff: I have received funding for research from Bristol Myers Squibb, and hold stocks in BMS; 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; M. Voss: Dr. Voss reports grants from BMS, outside the submitted work; P. Sharma: I have served as a consultant for: MedImmune, GSK, BMS, Jounce, Janssen, Pfizer, and Helsinn Therapeutics. I also own stock in Jounce; D. Heng: Has worked as a consultant for the following: BMS, Bayer, Pfizer, Novartis; Y. Shen: I am an employee of Bristol-Myers Squibb, and immediate family member employed at BMS; J. Kurland: I am an employee of and have stock or other ownership interest in BMS; P. Gagnier: 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.