Nivolumab for metastatic renal cell carcinoma

Results of a randomized phase II trial

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 Logan, Kim A. Margolin, Elizabeth R. Plimack, Alexandre M. Lambert, Ian M. Waxman, Hans J. Hammers

Research output: Contribution to journalArticle

511 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)1430-1437
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number13
DOIs
StatePublished - May 1 2015

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Renal Cell Carcinoma
Disease-Free Survival
Safety
Vascular Endothelial Growth Factor A
Fatigue
nivolumab
Immunoglobulins
Survival Rate
T-Lymphocytes
Survival
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Motzer, R. J., Rini, B. I., McDermott, D. F., Redman, B. G., Kuzel, T. M., Harrison, M. R., ... Hammers, H. J. (2015). Nivolumab for metastatic renal cell carcinoma: Results of a randomized phase II trial. Journal of Clinical Oncology, 33(13), 1430-1437. https://doi.org/10.1200/JCO.2014.59.0703

Nivolumab for metastatic renal cell carcinoma : Results of a randomized phase II trial. / Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

In: Journal of Clinical Oncology, Vol. 33, No. 13, 01.05.2015, p. 1430-1437.

Research output: Contribution to journalArticle

Motzer, RJ, Rini, BI, McDermott, DF, Redman, BG, Kuzel, TM, Harrison, MR, Vaishampayan, UN, Drabkin, HA, George, S, Logan, T, Margolin, KA, Plimack, ER, Lambert, AM, Waxman, IM & Hammers, HJ 2015, 'Nivolumab for metastatic renal cell carcinoma: Results of a randomized phase II trial', Journal of Clinical Oncology, vol. 33, no. 13, pp. 1430-1437. https://doi.org/10.1200/JCO.2014.59.0703
Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR et al. Nivolumab for metastatic renal cell carcinoma: Results of a randomized phase II trial. Journal of Clinical Oncology. 2015 May 1;33(13):1430-1437. https://doi.org/10.1200/JCO.2014.59.0703
Motzer, Robert J. ; Rini, Brian I. ; McDermott, David F. ; Redman, Bruce G. ; Kuzel, Timothy M. ; Harrison, Michael R. ; Vaishampayan, Ulka N. ; Drabkin, Harry A. ; George, Saby ; Logan, Theodore ; Margolin, Kim A. ; Plimack, Elizabeth R. ; Lambert, Alexandre M. ; Waxman, Ian M. ; Hammers, Hans J. / Nivolumab for metastatic renal cell carcinoma : Results of a randomized phase II trial. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 13. pp. 1430-1437.
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AU - Kuzel, Timothy M.

AU - Harrison, Michael R.

AU - Vaishampayan, Ulka N.

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AU - Logan, Theodore

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AU - Lambert, Alexandre M.

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