Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results

Padmanee Sharma, Arlene Siefker-Radtke, Filippo de Braud, Umberto Basso, Emiliano Calvo, Petri Bono, Michael A Morse, Paolo A Ascierto, Jose Lopez-Martin, Peter Brossart, Kristoffer Rohrberg, Begoña Mellado, Bruce S Fischer, Stephanie Meadows-Shropshire, Abdel Saci, Margaret K Callahan, Jonathan Rosenberg

Research output: Contribution to journalArticle

Abstract

PURPOSE: CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.

METHODS: Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.

RESULTS: Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.

CONCLUSION: With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.

Original languageEnglish
Pages (from-to)JCO1900538
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
DOIs
Publication statusPublished - 2019

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Carcinoma
Platinum
Immunotherapy
Multicenter Studies
Disease Progression
Pneumonia
Research Personnel
ipilimumab
nivolumab
Safety
Therapeutics

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Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma : CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. / Sharma, Padmanee; Siefker-Radtke, Arlene; de Braud, Filippo; Basso, Umberto; Calvo, Emiliano; Bono, Petri; Morse, Michael A; Ascierto, Paolo A; Lopez-Martin, Jose; Brossart, Peter; Rohrberg, Kristoffer; Mellado, Begoña; Fischer, Bruce S; Meadows-Shropshire, Stephanie; Abdel Saci; Callahan, Margaret K; Rosenberg, Jonathan.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019, p. JCO1900538.

Research output: Contribution to journalArticle

Sharma, P, Siefker-Radtke, A, de Braud, F, Basso, U, Calvo, E, Bono, P, Morse, MA, Ascierto, PA, Lopez-Martin, J, Brossart, P, Rohrberg, K, Mellado, B, Fischer, BS, Meadows-Shropshire, S, Abdel Saci, Callahan, MK & Rosenberg, J 2019, 'Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, pp. JCO1900538. https://doi.org/10.1200/JCO.19.00538
Sharma, Padmanee ; Siefker-Radtke, Arlene ; de Braud, Filippo ; Basso, Umberto ; Calvo, Emiliano ; Bono, Petri ; Morse, Michael A ; Ascierto, Paolo A ; Lopez-Martin, Jose ; Brossart, Peter ; Rohrberg, Kristoffer ; Mellado, Begoña ; Fischer, Bruce S ; Meadows-Shropshire, Stephanie ; Abdel Saci ; Callahan, Margaret K ; Rosenberg, Jonathan. / Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma : CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; pp. JCO1900538.
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title = "Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results",
abstract = "PURPOSE: CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.METHODS: Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.RESULTS: Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6{\%}, 26.9{\%}, and 38.0{\%} in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9{\%}), 32 (30.8{\%}), and 36 (39.1{\%}) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.CONCLUSION: With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.",
author = "Padmanee Sharma and Arlene Siefker-Radtke and {de Braud}, Filippo and Umberto Basso and Emiliano Calvo and Petri Bono and Morse, {Michael A} and Ascierto, {Paolo A} and Jose Lopez-Martin and Peter Brossart and Kristoffer Rohrberg and Bego{\~n}a Mellado and Fischer, {Bruce S} and Stephanie Meadows-Shropshire and {Abdel Saci} and Callahan, {Margaret K} and Jonathan Rosenberg",
year = "2019",
doi = "10.1200/JCO.19.00538",
language = "English",
pages = "JCO1900538",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",

}

TY - JOUR

T1 - Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma

T2 - CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results

AU - Sharma, Padmanee

AU - Siefker-Radtke, Arlene

AU - de Braud, Filippo

AU - Basso, Umberto

AU - Calvo, Emiliano

AU - Bono, Petri

AU - Morse, Michael A

AU - Ascierto, Paolo A

AU - Lopez-Martin, Jose

AU - Brossart, Peter

AU - Rohrberg, Kristoffer

AU - Mellado, Begoña

AU - Fischer, Bruce S

AU - Meadows-Shropshire, Stephanie

AU - Abdel Saci, null

AU - Callahan, Margaret K

AU - Rosenberg, Jonathan

PY - 2019

Y1 - 2019

N2 - PURPOSE: CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.METHODS: Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.RESULTS: Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.CONCLUSION: With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.

AB - PURPOSE: CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.METHODS: Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.RESULTS: Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.CONCLUSION: With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.

U2 - 10.1200/JCO.19.00538

DO - 10.1200/JCO.19.00538

M3 - Article

C2 - 31100038

SP - JCO1900538

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

ER -