Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: The checkmate 016 study

Hans J. Hammers, Elizabeth R. Plimack, Jeffrey R. Infante, Brian I. Rini, David F. McDermott, Lionel D. Lewis, Martin H. Voss, Padmanee Sharma, Sumanta K. Pal, Albiruni R. Abdul Razak, Christian Kollmannsberger, Daniel Y.C. Heng, Jennifer Spratlin, M. Brent McHenry, Asim Amin

Research output: Contribution to journalArticle

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Abstract

Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3% and 61.7% of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4% in both arms, with ongoing responses in 42.1% and 36.8% of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3% and 69.6% in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.

Original languageEnglish (US)
Pages (from-to)3851-3858
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number34
DOIs
StatePublished - Dec 1 2017

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Renal Cell Carcinoma
Safety
Survival
ipilimumab
nivolumab
Protein-Tyrosine Kinases
Melanoma
Therapeutics
Survival Rate
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma : The checkmate 016 study. / Hammers, Hans J.; Plimack, Elizabeth R.; Infante, Jeffrey R.; Rini, Brian I.; McDermott, David F.; Lewis, Lionel D.; Voss, Martin H.; Sharma, Padmanee; Pal, Sumanta K.; Abdul Razak, Albiruni R.; Kollmannsberger, Christian; Heng, Daniel Y.C.; Spratlin, Jennifer; Brent McHenry, M.; Amin, Asim.

In: Journal of Clinical Oncology, Vol. 35, No. 34, 01.12.2017, p. 3851-3858.

Research output: Contribution to journalArticle

Hammers, HJ, Plimack, ER, Infante, JR, Rini, BI, McDermott, DF, Lewis, LD, Voss, MH, Sharma, P, Pal, SK, Abdul Razak, AR, Kollmannsberger, C, Heng, DYC, Spratlin, J, Brent McHenry, M & Amin, A 2017, 'Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: The checkmate 016 study', Journal of Clinical Oncology, vol. 35, no. 34, pp. 3851-3858. https://doi.org/10.1200/JCO.2016.72.1985
Hammers, Hans J. ; Plimack, Elizabeth R. ; Infante, Jeffrey R. ; Rini, Brian I. ; McDermott, David F. ; Lewis, Lionel D. ; Voss, Martin H. ; Sharma, Padmanee ; Pal, Sumanta K. ; Abdul Razak, Albiruni R. ; Kollmannsberger, Christian ; Heng, Daniel Y.C. ; Spratlin, Jennifer ; Brent McHenry, M. ; Amin, Asim. / Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma : The checkmate 016 study. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 34. pp. 3851-3858.
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title = "Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma: The checkmate 016 study",
abstract = "Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3{\%} and 61.7{\%} of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4{\%} in both arms, with ongoing responses in 42.1{\%} and 36.8{\%} of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3{\%} and 69.6{\%} in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.",
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T1 - Safety and efficacy of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma

T2 - The checkmate 016 study

AU - Hammers, Hans J.

AU - Plimack, Elizabeth R.

AU - Infante, Jeffrey R.

AU - Rini, Brian I.

AU - McDermott, David F.

AU - Lewis, Lionel D.

AU - Voss, Martin H.

AU - Sharma, Padmanee

AU - Pal, Sumanta K.

AU - Abdul Razak, Albiruni R.

AU - Kollmannsberger, Christian

AU - Heng, Daniel Y.C.

AU - Spratlin, Jennifer

AU - Brent McHenry, M.

AU - Amin, Asim

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3% and 61.7% of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4% in both arms, with ongoing responses in 42.1% and 36.8% of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3% and 69.6% in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.

AB - Purpose Combination treatment with immune checkpoint inhibitors has shown enhanced antitumor activity compared with monotherapy in tumor types such as melanoma. The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). Safety and efficacy results from the nivolumab plus ipilimumab arms of the study are presented. Patients and Methods Patients with mRCC received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks until progression or toxicity. End points included safety (primary), objective response rate, and overall survival (OS). Results All patients in the N3I3 arm (n = 6) were censored at the time of analysis as a result of dose-limiting toxicity or other reasons. Forty-seven patients were treated in both the N3I1 and the N1I3 arm, and baseline patient characteristics were balanced between arms. Grade 3 to 4 treatment-related adverse events were reported in 38.3% and 61.7% of the patients in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, the confirmed objective response rate was 40.4% in both arms, with ongoing responses in 42.1% and 36.8% of patients in the N3I1 and N1I3 arms, respectively. The 2-year OS was 67.3% and 69.6% in the N3I1 and N1I3 arms, respectively. Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notable antitumor activity, and durable responses with promising OS in patients with mRCC.

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