Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01642004
First received: July 9, 2012
Last updated: March 16, 2016
Last verified: March 2016

July 9, 2012
March 16, 2016
September 2012
November 2014   (final data collection date for primary outcome measure)
  • Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
  • Overall Survival (OS) Rate in All Randomized Participants [ Time Frame: Randomization to 18 months post-randomization, up to June 2015 ] [ Designated as safety issue: No ]
    The overall survival rate is the probability that a participant will be alive at 6, 12, and 18 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
  • Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    The number of participants who died from any cause was reported for each arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
  • Objective Response Rate [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Objective Response Rate is defined as the number of subjects with a Best overall response (BOR) of CR or PR divided by the number of randomized subjects
  • Overall Survival [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Overall Survival is defined as the time from randomization to the date of death
Complete list of historical versions of study NCT01642004 on ClinicalTrials.gov Archive Site
  • Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]

    ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first.

    CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.

  • Time To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint [ Time Frame: Randomization until confirmed response, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.
  • Duration of Objective Response (DOR) in Months for All Confirmed Responders at Primary Endpoint [ Time Frame: Date of confirmed response to date of documented tumor progression, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]

    DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR).

    CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.

    Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment.

  • Progression-Free Survival (PFS) at Primary Endpoint [ Time Frame: Randomization to 12 months post-randomization, up to November 2014 ] [ Designated as safety issue: No ]
    PFS rate was defined as the probability that participants will experience no disease progression or death from any cause at a given time point following randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative radiation therapy (RT) of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy
  • Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. Participants underwent radiographic tumor assessments every 6 weeks (+/- 5 days) from week 9 (+/- 5 days) for the first year on treatment, then every 12 weeks after the first year on treatment until documented disease progression. The PFS curves were estimated using KM method. Two-sided 95% CI for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy.
  • Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 [ Time Frame: Randomization to Week 12 ] [ Designated as safety issue: No ]
    Disease-related symptom improvement rate by Week 12 was defined as the percentage of randomized participants who had a 10 point or greater decrease from baseline in average symptom burden index score at any time between randomization and Week 12. The participant portion of the Lung Cancer Symptom Scale (LCSS) consisted of 6 symptom-specific questions that addressed cough, dyspnea, fatigue, pain, hemoptysis, and anorexia, plus 3 summary items on symptom distress, interference with activity level, and global health-related Quality of Life (QoL). The scores range from 0 to 100, with 0 representing the best possible score and 100 being the worst possible score. The average symptom burden index score at each assessment was defined as the mean of the 6 symptom-specific questions of the LCSS. 95% CIs were computed using Clopper-Pearson Method.
  • Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    OS was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
  • Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CIs were computed using the Clopper and Pearson method.
  • Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 199 deaths, up to November 2014, approximately 25 months ] [ Designated as safety issue: No ]
    PFS time was measured for all randomized participants grouped by their baseline PD-L1 expression levels. PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. The PFS curves were estimated using KM method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy (including on-treatment palliative radiotherapy of non-target bone lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to subsequent anti-cancer therapy. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths.
  • The progression-free survival (PFS) of BMS-936558 versus docetaxel [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
  • Clinical benefit in terms of Objective response rate (ORR) and Overall survival (OS) of BMS-936558 versus docetaxel, in PD-L1 + versus PD-L1- protein expression subgroups [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
  • Duration of objective response in BMS-936558 and docetaxel groups [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Duration of objective response (DOOR) is defined as the time between the date of first response to the date of the first documented tumor progression or death due to any cause
  • Time to objective response in BMS-936558 and docetaxel groups [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Time to objective response (TTOR) is defined as the time from randomization to the date of the first documented Complete response (CR) or Partial response (PR)
  • Proportion of subjects exhibiting disease-related symptom progression, as measured by Lung Cancer Symptom Scale (LCSS), in BMS-936558 and docetaxel groups [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
Overall Survival (OS) Time in Months for All Randomized Participants at Updated Survival Follow-up [ Time Frame: Randomization until July 2015, approximately 33 months ] [ Designated as safety issue: No ]
OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Survival follow-up analysis occurred 7.4 months after Primary Endpoint was reached, representing a minimum OS follow-up time of 18.0 months.
Not Provided
 
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) (CheckMate 017)
An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC)
The purpose of the study is to compare the overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Squamous Cell Non-small Cell Lung Cancer
  • Biological: Nivolumab
    Other Name: BMS-936558
  • Drug: Docetaxel
    Other Name: Taxotere®
  • Experimental: Arm A: Nivolumab
    Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Intervention: Biological: Nivolumab
  • Experimental: Arm B: Docetaxel
    Docetaxel 75 mg/m2 solution intravenously every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Intervention: Drug: Docetaxel
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
352
January 2017
November 2014   (final data collection date for primary outcome measure)

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Men and women ≥18 years of age
  • Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease)
  • Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
  • Measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

  • Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent)
  • Subjects with carcinomatous meningitis
  • Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
  • Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Prior treatment on the first line study CA184104 first line NSCLC study
  • Prior treatment with Docetaxel
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Treatment with any investigational agent within 14 days of first administration of study treatment
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Canada,   Chile,   Czech Republic,   France,   Germany,   Hungary,   Ireland,   Italy,   Mexico,   Netherlands,   Peru,   Poland,   Romania,   Russian Federation,   Spain,   United Kingdom
Brazil,   Greece,   Norway,   South Africa,   Turkey
 
NCT01642004
CA209-017, 2011-004792-36
Yes
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP