Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC (CheckMate057)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01673867
First received: August 24, 2012
Last updated: January 29, 2016
Last verified: January 2016

August 24, 2012
January 29, 2016
October 2012
February 2015   (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 413 deaths, up to March 2015 (approximately 29 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 380 deaths, with the actual analysis occurring at 413 deaths.
  • One-year Overall Survival (OS) Rate in All Randomized Participants [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The one-year overall survival rate is a percentage, representing the fraction of all randomized participants who were alive following one year of treatment. 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 413 deaths, up to March 2015 (approximately 29 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 380 deaths, with the actual analysis occurring at 413 deaths.
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 NCT01673867 on ClinicalTrials.gov Archive Site
  • Objective Response Rate (ORR) in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]

    ORR was defined as the percentage of 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.

  • 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 or death, up to March 2015 (approximately 29 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.

  • Time To Response (TTR) in Months for All Confirmed Responders at Primary Endpoint [ Time Frame: Randomization until confirmed response, up to March 2015 (approximately 29 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.
  • Progression-Free Survival (PFS) Rate at 12 Months [ Time Frame: Randomization to 12 months ] [ Designated as safety issue: No ]
    PFS rate was defined as the percentage of participants experiencing no disease progression or death from any cause at 12 months after randomization. Progression was assessed by investigators according to RECIST v1.1. 95% CIs were estimated using the Kaplan-Meier method.
  • Progression-Free Survival (PFS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 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% CIs for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
  • 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 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. 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. Interim analysis (Primary Endpoint) was planned to occur after at least 380 deaths, with the actual analysis occurring at 413 deaths.
  • Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants at Primary Endpoint [ Time Frame: Randomization until 413 deaths, up to March 2015 (approximately 29 months) ] [ Designated as safety issue: No ]
    ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. 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. 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). 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.
  • Objective response rate of BMS-936558 versus Docetaxel [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Objective response rate is defined as the proportion of all randomized subjects whose best overall response (BOR) from baseline is either a Complete response (CR) or Partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Progression-free survival (PFS) of BMS-936558 versus Docetaxel [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause
  • Clinical benefit of BMS-936558 versus Docetaxel, in PD-L1 + versus PD-L1-protein expression subgroups [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • 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 ]
Not Provided
Not Provided
 
Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC
An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)
The purpose of the study is to compare the overall survival of BMS-936558 (Nivolumab) as compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy
CheckMate 057: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 057
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-Squamous Cell Non-small Cell Lung Cancer
  • Biological: Nivolumab
    Other Name: BMS-936558 (Anti-PD1)
  • 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
  • Active Comparator: Arm B: Docetaxel
    Docetaxel 75 mg/m^2 concentrate for solution for intravenous infusion every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
    Intervention: Drug: Docetaxel
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
792
May 2016
February 2015   (final data collection date for primary outcome measure)

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

Inclusion Criteria:

  • Men & women ≥18 years of age
  • Subjects with histologically or cytologically-documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as second or third line of treatment for 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 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 asymptomatic or 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 ≤10mg daily prednisone (or equivalent)
  • Subjects with carcinomatous meningitis
  • Subjects with active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment 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 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Prior treatment with Docetaxel
  • 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,   Brazil,   Canada,   Chile,   Czech Republic,   France,   Germany,   Hong Kong,   Hungary,   Italy,   Mexico,   Norway,   Peru,   Poland,   Romania,   Russian Federation,   Singapore,   Spain,   Switzerland
South Africa,   Turkey
 
NCT01673867
CA209-057, 2012-002472-14
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
January 2016

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