1050O - Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC)

Date 27 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Cancer Immunology and Immunotherapy
Presenter Hans Hammers
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors H. Hammers1, E.R. Plimack2, J.R. Infante3, M. Ernstoff4, B.I. Rini5, D.F. McDermott6, A.R.A. Razak7, S. Pal8, M. Voss9, P. Sharma10, C.K. Kollmannsberger11, D. Heng12, Y. Shen13, J. Spratlin14, J. Kurland15, P. Gagnier15, A. Amin16
  • 1Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 21231 - Baltimore/US
  • 2Oncology, Fox Chase Cancer Center, 19111 - Philadelphia/US
  • 3Tennessee Oncology, Pllc, Sarah Cannon Research Institute, 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
  • 8Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte/US
  • 9Oncology, Memorial Sloan Kettering Cancer Center, New York/US
  • 10Md Anderson Cancer Center, University of Texas, Houston/US
  • 11Medical Oncology, British Columbia Cancer Agency, Vancouver/CA
  • 12Tom Baker Cancer Center, University of Calgary, Calgary/CA
  • 13Biostatistics, Bristol-Myers Squibb, Princeton/US
  • 14Cross Cancer Institute, University of Alberta, Edmonton/CA
  • 15Bio Research, Bristol-Myers Squibb, Princeton/US
  • 16Medical Oncology, Levine Cancer Institute, 28204 - Charlotte/US

 

Abstract

Aim

Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has shown durable responses and encouraging overall survival (OS) data in mRCC. IPI, a fully human monoclonal antibody to CTLA-4, improved OS in melanoma and has antitumor activity in mRCC. The combination of these agents showed encouraging antitumor activity and an acceptable safety profile in advanced melanoma. We report preliminary results of this combination in mRCC.

Methods

Patients (pts) with mRCC were randomized to nivolumab 3 mg/kg + IPI 1 mg/kg (arm N3 + I1) or nivolumab 1 mg/kg + IPI 3 mg/kg (N1 + I3) IV every 3 wk for 4 doses then nivolumab 3 mg/kg IV every 2 wk until progression/toxicity (protocol-defined post-progression treatment allowed). The primary objective was to assess safety; secondary objective was to assess efficacy (RECIST 1.1).

Results

21 and 23 pts were randomized to the N3 + I1 and N1 + I3 arms, respectively. Most pts (n = 35; 80%) had prior systemic therapy (N3 + I1: 17; N1 + I3: 18). Treatment-related adverse events (AEs) were seen in 39 pts (89%); 8 pts (18%; N3 + I1: 2; N1 + I3: 6) discontinued due to related AEs. Grade 3-4-related AEs occurred in 20 pts (46%; N3 + I1: 6; N1 + I3: 14), most commonly ↑ lipase (21%, n = 9), ↑ ALT (14%, n = 6), diarrhea (9%, n = 4), and ↑ AST (7%, n = 3). No grade 3-4 pneumonitis was seen. Objective response rate (ORR) was 43% (N3 + I1) and 48% (N1 + I3); median duration of response (DOR) was 31.1 wk (7 ongoing) in N3 + I1 and not reached (9 ongoing) in N1 + I3 (Table). Responses occurred by first tumor assessment (wk 6) in 44% of pts in the N3 + I1 arm and 55% of pts in the N1 + I3 arm. Stable disease (SD) as best overall response was seen in 5 (24%) (N3 + I1) and 8 (35%) (N1 + I3) pts.  

Arm N3 + I1 n = 21 Arm N1 + I3 n = 23
ORR, n (%) 9 (43) 11 (48)
SD, n (%) 5 (24) 8 (35)
DOR, range (wk) 4.1+ - 42.1+ 12.1+ - 35.1 +
Median progression-free survival, wk (95% CI) 36.6 (6.0, ) 38.3 (18.3, )
CI, confidence interval

Conclusions

Nivolumab + IPI showed acceptable safety and encouraging antitumor activity in mRCC, with most responses ongoing. Studies are ongoing to explore this combination in a Phase III trial.

Disclosure

H. Hammers: Has received Honoraria from Ono Pharma USA; E.R. Plimack: Has 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: I have 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 BM.; 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; A. Amin: I have worked as a consultant/ in an advisory capacity to: Bristol Myers Squibb. I have received Honoraria from: Bristol Myers Squibb. All other authors have declared no conflicts of interest.