Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): A phase 2, single-arm trial

Naiyer A. Rizvi, Julien Mazières, David Planchard, Thomas E. Stinchcombe, Grace K. Dy, Scott J. Antonia, Leora Horn, Hervé Lena, Elisa Minenza, Bertrand Mennecier, Gregory A. Otterson, Luis T. Campos, David R. Gandara, Benjamin P. Levy, Suresh G. Nair, Gérard Zalcman, Jürgen Wolf, Pierre Jean Souquet, Editta Baldini, Federico CappuzzoChristos Chouaid, Afshin Dowlati, Rachel Sanborn, Ariel Lopez-Chavez, Christian Grohe, Rudolf M. Huber, Christopher T. Harbison, Christine Baudelet, Brian J. Lestini, Suresh S. Ramalingam

Research output: Contribution to journalArticle

828 Citations (Scopus)

Abstract

Background: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding: Bristol-Myers Squibb.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalThe Lancet Oncology
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Safety
Advisory Committees
Radiology
nivolumab
Pneumonia
Therapeutics
Cancer Care Facilities
Private Hospitals
Poisons
Italy
France
Fatigue
Germany
Comorbidity
Diarrhea
Immunoglobulin G
Stroke
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063) : A phase 2, single-arm trial. / Rizvi, Naiyer A.; Mazières, Julien; Planchard, David; Stinchcombe, Thomas E.; Dy, Grace K.; Antonia, Scott J.; Horn, Leora; Lena, Hervé; Minenza, Elisa; Mennecier, Bertrand; Otterson, Gregory A.; Campos, Luis T.; Gandara, David R.; Levy, Benjamin P.; Nair, Suresh G.; Zalcman, Gérard; Wolf, Jürgen; Souquet, Pierre Jean; Baldini, Editta; Cappuzzo, Federico; Chouaid, Christos; Dowlati, Afshin; Sanborn, Rachel; Lopez-Chavez, Ariel; Grohe, Christian; Huber, Rudolf M.; Harbison, Christopher T.; Baudelet, Christine; Lestini, Brian J.; Ramalingam, Suresh S.

In: The Lancet Oncology, Vol. 16, No. 3, 01.03.2015, p. 257-265.

Research output: Contribution to journalArticle

Rizvi, NA, Mazières, J, Planchard, D, Stinchcombe, TE, Dy, GK, Antonia, SJ, Horn, L, Lena, H, Minenza, E, Mennecier, B, Otterson, GA, Campos, LT, Gandara, DR, Levy, BP, Nair, SG, Zalcman, G, Wolf, J, Souquet, PJ, Baldini, E, Cappuzzo, F, Chouaid, C, Dowlati, A, Sanborn, R, Lopez-Chavez, A, Grohe, C, Huber, RM, Harbison, CT, Baudelet, C, Lestini, BJ & Ramalingam, SS 2015, 'Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): A phase 2, single-arm trial', The Lancet Oncology, vol. 16, no. 3, pp. 257-265. https://doi.org/10.1016/S1470-2045(15)70054-9
Rizvi, Naiyer A. ; Mazières, Julien ; Planchard, David ; Stinchcombe, Thomas E. ; Dy, Grace K. ; Antonia, Scott J. ; Horn, Leora ; Lena, Hervé ; Minenza, Elisa ; Mennecier, Bertrand ; Otterson, Gregory A. ; Campos, Luis T. ; Gandara, David R. ; Levy, Benjamin P. ; Nair, Suresh G. ; Zalcman, Gérard ; Wolf, Jürgen ; Souquet, Pierre Jean ; Baldini, Editta ; Cappuzzo, Federico ; Chouaid, Christos ; Dowlati, Afshin ; Sanborn, Rachel ; Lopez-Chavez, Ariel ; Grohe, Christian ; Huber, Rudolf M. ; Harbison, Christopher T. ; Baudelet, Christine ; Lestini, Brian J. ; Ramalingam, Suresh S. / Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063) : A phase 2, single-arm trial. In: The Lancet Oncology. 2015 ; Vol. 16, No. 3. pp. 257-265.
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abstract = "Background: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5{\%}, 95{\%} CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95{\%} CI 8·31-not applicable); 13 (77{\%}) of 17 of responses were ongoing at the time of analysis. 30 (26{\%}) of 117 patients had stable disease (median duration 6·0 months, 95{\%} CI 4·7-10·9). 20 (17{\%}) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4{\%}] of 117 patients), pneumonitis (four [3{\%}]), and diarrhoea (three [3{\%}]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding: Bristol-Myers Squibb.",
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TY - JOUR

T1 - Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063)

T2 - A phase 2, single-arm trial

AU - Rizvi, Naiyer A.

AU - Mazières, Julien

AU - Planchard, David

AU - Stinchcombe, Thomas E.

AU - Dy, Grace K.

AU - Antonia, Scott J.

AU - Horn, Leora

AU - Lena, Hervé

AU - Minenza, Elisa

AU - Mennecier, Bertrand

AU - Otterson, Gregory A.

AU - Campos, Luis T.

AU - Gandara, David R.

AU - Levy, Benjamin P.

AU - Nair, Suresh G.

AU - Zalcman, Gérard

AU - Wolf, Jürgen

AU - Souquet, Pierre Jean

AU - Baldini, Editta

AU - Cappuzzo, Federico

AU - Chouaid, Christos

AU - Dowlati, Afshin

AU - Sanborn, Rachel

AU - Lopez-Chavez, Ariel

AU - Grohe, Christian

AU - Huber, Rudolf M.

AU - Harbison, Christopher T.

AU - Baudelet, Christine

AU - Lestini, Brian J.

AU - Ramalingam, Suresh S.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Background: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding: Bristol-Myers Squibb.

AB - Background: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding: Bristol-Myers Squibb.

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