Nivolumab for metastatic renal cell carcinoma (mRCC): Results of a randomized, dose-ranging phase II trial.

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Clinical Science Symposium, Unleashing the Immune System in Genitourinary Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5009)
Robert J. Motzer, Brian I. Rini, David F. McDermott, Bruce G. Redman, Timothy Kuzel, Michael Roger Harrison, Ulka N. Vaishampayan, Harry A. Drabkin, Saby George, Theodore F. Logan, Kim Allyson Margolin, Elizabeth R. Plimack, Ian Waxman, Alexandre Lambert, Hans J. Hammers; Memorial Sloan-Kettering Cancer Center, New York, NY; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Northwestern University, Chicago, IL; Duke University Medical Center, Durham, NC; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Medical University of South Carolina, Charleston, SC; Roswell Park Cancer Institute, Buffalo, NY; Indiana University, Indiana Cancer Pavillion, Indianapolis, IN; Seattle Cancer Care Alliance, Seattle, WA; Fox Chase Cancer Center, Philadelphia, PA; Bristol-Myers Squibb, Princeton, NJ; Bristol-Myers Squibb, Paris, France; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD

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Abstract Disclosures


Background: Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, restores T-cell immune activity and showed objective responses in mRCC in a phase I trial (NEJM 366:2443). This phase II trial (NCT01354431) assesses three nivolumab doses in mRCC patients (pts) pretreated with agents targeting the VEGF pathway. Methods: Pts with clear-cell mRCC (≥1 agent targeting VEGF pathway; ≤3 prior systemic therapies) were randomized (blinded 1:1:1) to nivolumab 0.3, 2 or 10 mg/kg IV Q3W until progression or toxicity. The primary objective was to evaluate the dose-response relationship measured by progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR) and safety assessment. Results: All pts (N=168) received prior systemic therapy (70% received ≥2) including VEGFR TKIs (98%), mTOR inhibitors (38%) and immunotherapy (24%). 25% were MSKCC poor risk. All had >16 months of follow-up. No dose-response relationship was noted for PFS (stratified trend test, P=0.9). PFS and ORR were similar across doses (Table). For 0.3 mg/kg, median duration of response was 15.7 months and median OS was 18.2 months; for other doses medians were not reached. 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. Conclusions: Antitumor activity was observed with nivolumab in this pretreated mRCC population including objective responses of long duration. No dose-response relationship for PFS was noted and the safety profile was acceptable. Median OS was 18.2 months for the 0.3 mg/kg dose and was not reached for 2 or 10 mg/kg; updated OS will be presented. Clinical trial information: NCT01354431.

0.3 mg/kg
2 mg/kg
10 mg/kg
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 OS, months (80% CI) 18.2 (16.7, NR) NR NR
Treatment-related AE, n (%)
Grade 3–4
44 (75)
3 (5)
36 (67)
9 (17)
42 (78)
7 (13)

a Safety analysis included 59 treated pts; CI=confidence interval; NR=not reached.