Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

• DOI: 10.1200/jco.2014.59.0703
• Publication Date: 2014-12-02T04:53:19Z
• Authors: Robert J. Motzer; Brian I. Rini; David F. McDermott; Bruce G. Redman; Timothy M. Kuzel; Michael R. Harrison; Ulka N. Vaishampayan; Harry A. Drabkin; Saby George; Theodore F. Logan; Kim A. Margolin; Elizabeth R. Plimack; Alexandre M. Lambert; Ian M. Waxman; Hans J. Hammers
• Keywords: Male; Canada; Dose-Response Relationship, Drug; Antibodies, Monoclonal; Antineoplastic Agents; Kaplan-Meier Estimate; Middle Aged; B7-H1 Antigen; Disease-Free Survival; Drug Administration Schedule; Kidney Neoplasms; 3. Good health; 03 medical and health sciences; Nivolumab; 0302 clinical medicine; Italy; Disease Progression; Humans; Administration, Intravenous; Female; Carcinoma, Renal Cell; Finland; Aged

Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients Methods clear-cell mRCC previously treated agents targeting vascular endothelial growth factor pathway were randomly assigned (blinded ratio 1:1:1) to 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was evaluate relationship as measured by progression-free survival (PFS); secondary end points included response rate (ORR), overall (OS), safety. Results A total 168 0.3- (n = 60), 2- 54), 10-mg/kg 54) cohorts. One hundred eighteen (70%) had received more than one prior systemic regimen. Median PFS 2.7, 4.0, 4.2 months, respectively (P .9). Respective ORRs 20%, 22%, 20%. OS 18.2 months (80% CI, 16.2 24.0 months), 25.5 19.8 28.8 24.7 15.3 26.0 respectively. most common treatment-related adverse event (AE) fatigue (24%, 35%, respectively). Nineteen (11%) experienced grade 4 AEs. Conclusion demonstrated activity manageable profile across three doses studied mRCC. No detected PFS. These efficacy results support study III setting.