Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00527735
First received: September 7, 2007
Last updated: June 11, 2012
Last verified: June 2012
Results First Received: February 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Lung Cancer
Small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Interventions: Drug: Ipilimumab
Drug: Placebo
Drug: Paclitaxel
Drug: Carboplatin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 334 participants enrolled in this study, 331 received treatment. One patient with nonsmall-cell lung cancer, randomized to the sequential arm but mistakenly treated with concurrent therapy, is included in the sequential arm for efficacy results and in the concurrent arm for safety results.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until progressive disease (PD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Participant Flow:   Overall Study
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
STARTED     113 [1]   109 [1]   109 [1]
COMPLETED     5 [2]   2 [2]   2 [2]
NOT COMPLETED     108     107     107  
Disease progression                 47                 61                 53  
Death                 23                 13                 15  
Completed treatment in treatment phase                 14                 13                 18  
Adverse Event                 10                 6                 7  
Not identified                 5                 5                 5  
Withdrawal by Subject                 5                 4                 3  
No longer met study criteria                 2                 2                 1  
Lost to Follow-up                 0                 0                 3  
Poor compliance or noncompliance                 0                 1                 1  
Completed treatment during maintenance                 2                 2                 1  
[1] Treated
[2] Still on treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (concurrent). The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes every 3 weeks. Participants who experienced clinical benefit on treatment phase without intolerable toxicity were allowed to continue in the maintenance phase, receiving additional ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until immune-related progressive disease (irPD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (sequential). The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes every 3 weeks. Participants who experienced clinical benefit on treatment phase without intolerable toxicity were allowed to continue in the maintenance phase, receiving additional ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who experienced clinical benefit on treatment phase without intolerable toxicity could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Total Total of all reporting groups

Baseline Measures
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin     Total  
Number of Participants  
[units: participants]
  113     110     111     334  
Age, Customized [1]
[units: Participants]
       
Younger than 65 years     79     73     76     228  
65 years and older     34     37     35     106  
Gender  
[units: Participants]
       
Female     27     29     29     85  
Male     86     81     82     249  
Age Customized, by Disease Type [2]
[units: Participants]
       
Younger than 65 years (NSCLC patients)     44     44     40     128  
65 years and older (NSCLC patients)     26     24     26     76  
Younger than 65 years (SCLC patients)     35     29     36     100  
65 years and older (SCLC patients)     8     13     9     30  
Gender, by Disease Type [2]
[units: Participants]
       
Female (NSCLC patients)     17     19     17     53  
Male (NSCLC patients)     53     49     49     151  
Female (SCLC patients)     10     10     12     32  
Male (SCLC patients)     33     32     33     98  
Disease Stage at Study Entry [3]
[units: Participants]
       
Stage IIIB (NSCLC patients)     11     7     17     35  
Stage IV (NSCLC patients)     59     61     49     169  
Extensive (SCLC patients)     43     42     44     129  
Recurrent disease (SCLC patients)     0     0     1     1  
Cell Type [2]
[units: Participants]
       
Adenocarcinoma (NSCLC patients)     35     30     38     103  
Bronchoalveolar carcinoma (NSCLC patients)     1     1     0     2  
Large-cell carcinoma (NSCLC patients)     6     11     7     24  
Other (NSCLC patients)     6     4     3     13  
Squamous-cell carcinoma (NSCLC patients)     21     21     15     57  
Unknown (NSCLC patients)     1     1     3     5  
Other (SCLC patients)     2     2     0     4  
Small-cell carcinoma (SCLC patients)     41     38     45     124  
Unknown (SCLC patients)     0     1     0     1  
Not reported (SCLC patients)     0     1     0     1  
[1] Age of participants who received treatment.
[2] NSCLC=nonsmall-cell lung cancer; SCLC=small-cell lung cancer
[3] NSCLC=nonsmall-cell lung cancer; SCLC=small-cell lung cancer. Staging of NSCLC is based on the findings of several clinical tests, including magnetic resonance imaging scans and fine needle biopsy. Stages range from 1 (best prognosis) to IV (worst prognosis). Stage I cancer is confined to the lung. Stages II and III cancers are locally advanced. Stage IV cancer has spread outside the lung to other organs. SCLC is staged using a 2-tiered system: Limited stage SCLC is confined to its area of origin in the lung and lumph nodes. Extensive-stage SCLC has spread beyond the lung to other organs.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)   [ Time Frame: Tumor assessed at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until immune-related Progressive Disease (irPD) or death (of censored, maximum reached: 16.5 months) ]

Measure Type Primary
Measure Title Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
Measure Description irPFS is defined as the time between the randomization date and date of immune-related Progressive Disease (irPD) (at least 25% increase percentage change in total tumor burden, including new lesions) or death, whichever occurs first. For patients with no recorded postbaseline tumor assessments, irPFS is censored at randomization. Participant who die without reported irPD are considered to have progressed on the date of death. For those who remain alive and have no irPD, irPFS is censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.
Time Frame Tumor assessed at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until immune-related Progressive Disease (irPD) or death (of censored, maximum reached: 16.5 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until immune-related progressive disease (irPD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  70     68     66  
Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)  
[units: Months]
Median ( 95% Confidence Interval )
  5.52  
  ( 4.17 to 6.74 )  
  5.68  
  ( 4.76 to 7.79 )  
  4.63  
  ( 4.14 to 5.52 )  


Statistical Analysis 1 for Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.1302
Hazard Ratio (HR) [4] 0.806
95% Confidence Interval ( 0.553 to 1.174 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
Groups [1] Ipilimumab + Paclitaxel/Carboplatin (Sequential) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.0473
Hazard Ratio (HR) [4] 0.724
95% Confidence Interval ( 0.495 to 1.059 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria   [ Time Frame: Randomization date to date of progression or death (of censored, maximum reached: 13.6 months) ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
Measure Description By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.
Time Frame Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All NSCLC participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  70     68     66  
Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria  
[units: Months]
Mean ( 95% Confidence Interval )
  4.11  
  ( 2.76 to 5.32 )  
  5.13  
  ( 4.17 to 5.72 )  
  4.21  
  ( 2.76 to 5.32 )  


Statistical Analysis 1 for Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] One-sided log rank
P Value [3] 0.2502
Hazard Ratio (HR) [4] 0.882
95% Confidence Interval ( 0.612 to 1.271 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
Groups [1] Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) vs. Placebo + Paclitaxel/Carboplatin
Method [2] One-sided log rank
P Value [3] 0.0240
Hazard Ratio (HR) [4] 0.691
95% Confidence Interval ( 0.478 to 0.999 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Overall Survival in Participants With NSCLC   [ Time Frame: Randomization date to date of death (of censored, maximum reached: 26.5 months) ]

Measure Type Secondary
Measure Title Overall Survival in Participants With NSCLC
Measure Description Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.
Time Frame Randomization date to date of death (of censored, maximum reached: 26.5 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All NSCLC participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  70     68     66  
Overall Survival in Participants With NSCLC  
[units: Months]
Median ( 95% Confidence Interval )
  9.69  
  ( 7.59 to 12.48 )  
  12.22  
  ( 9.26 to 14.39 )  
  8.28  
  ( 6.80 to 12.39 )  


Statistical Analysis 1 for Overall Survival in Participants With NSCLC
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.4759
Hazard Ratio (HR) [4] 0.988
95% Confidence Interval ( 0.669 to 1.460 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Overall Survival in Participants With NSCLC
Groups [1] Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.2340
Hazard Ratio (HR) [4] 0.866
95% Confidence Interval ( 0.587 to 1.278 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC   [ Time Frame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance ]

Measure Type Secondary
Measure Title Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC
Measure Description mWHO criteria define BORR as the number of patients with best overall response of Complete Response (CR) or Partial Response (PR), divided by the total number of participants in the data set (multiplied by 100 for percentage). CR=Complete disappearance of all index lesions; PR=decrease from baseline of >=50% in the sum of products of the 2 largest perpendicular diameters of all index lesions. Independent review committee performed tumor assessment.
Time Frame Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  113     110     111  
Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
     
BORR (mWHO criteria) NSCLC cohort (n=70, 68, 66)     21.4  
  ( 12.5 to 32.29 )  
  32.4  
  ( 21.5 to 44.8 )  
  13.6  
  ( 6.4 to 24.3 )  
BORR (mWHO criteria) SCLC cohort (n=43, 42, 45)     32.6  
  ( 19.1 to 48.5 )  
  57.1  
  ( 41.0 to 72.3 )  
  48.9  
  ( 33.7 to 64.2 )  

No statistical analysis provided for Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC



5.  Secondary:   Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)   [ Time Frame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance ]

Measure Type Secondary
Measure Title Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)
Measure Description irBORR=number of participants with irBORR of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), divided by total participants in the data set. irCR=Complete disappearance of all index lesions. irPR=Decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index and of all new measurable lesions. Independent review committee performed the tumor assessments.
Time Frame Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  113     110     111  
Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
     
irBORR ( irRC) NSCLC cohort (n=70, 68, 66)     21.4  
  ( 12.5 to 32.29 )  
  32.4  
  ( 21.5 to 44.8 )  
  18.2  
  ( 9.8 to 29.6 )  
irBORR (irRC) SCLC cohort (n=43, 42, 45)     48.8  
  ( 33.3 to 64.5 )  
  71.4  
  ( 55.4 to 84.3 )  
  53.3  
  ( 37.9 to 68.3 )  

No statistical analysis provided for Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)



6.  Secondary:   Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC   [ Time Frame: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until irPD, progressive disease, or death (maximum reached: 22 months) ]

Measure Type Secondary
Measure Title Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC
Measure Description irDCR is defined as the proportion of participants whose immune-related best overall response is irPR, irCR, or immune-related Stable Disease (irSD) in the analysis data set. irSD=Does not meet criteria for irCR or irPR, in the absence of progressive disease. By mWHO criteria, DCR is defined as the proportion of participants whose best overall response is PR, CR, or SD in the analysis data set. SD=A decrease or tumor stabilization of 1 or more nonindex lesions. Independent review committee assessed response.
Time Frame Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until irPD, progressive disease, or death (maximum reached: 22 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  113     110     111  
Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC  
[units: Percent of participants]
Number ( 95% Confidence Interval )
     
irDCR (irRC) NSCLC cohort (n=70, 68, 66)     70.0  
  ( 57.9 to 80.4 )  
  86.8  
  ( 76.4 to 93.8 )  
  81.8  
  ( 70.4 to 90.2 )  
DCR (mWHO criteria) NSCLC cohort (n=70, 68, 66)     57.1  
  ( 44.7 to 68.9 )  
  77.9  
  ( 66.2 to 87.1 )  
  72.7  
  ( 60.4 to 83.0 )  
rDCR (irRC) SCLC cohort (n=43, 42, 45)     81.4  
  ( 66.6 to 91.6 )  
  92.9  
  ( 80.5 to 98.5 )  
  95.6  
  ( 84.9 to 99.5 )  
DCR (mWHO criteria) SCLC cohort (n=43, 42, 45)     69.8  
  ( 53.9 to 82.8 )  
  81.0  
  ( 65.9 to 91.4 )  
  93.3  
  ( 81.7 to 98.6 )  

No statistical analysis provided for Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC



7.  Secondary:   Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC   [ Time Frame: Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months) ]

Measure Type Secondary
Measure Title Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC
Measure Description irDoR is defined as the time between the date of response of confirmed irCR or irPR and the date of irPD or death, whichever occurs first. For those participants who remain alive and did progress following response, irDoR was censored on the date of last evaluable tumor assessment. By mWHO criteria, DoR is defined as the time between the date of response of confirmed CR or PR and the date of PD or death, whichever occurs first. For those who remain alive and did not progress following response, DoR was censored on the date of last evaluable tumor assessment.
Time Frame Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  113     110     111  
Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC  
[units: Months]
Median ( 95% Confidence Interval )
     
irDoR (irRC) NSCLC cohort (n=70, 63, 62)     6.70  
  ( 4.21 to 8.51 )  
  5.55  
  ( 4.27 to 6.74 )  
  4.01  
  ( 4.01 to 5.72 )  
DoR (mWHO criteria) NSCLC cohort (n=70, 63, 62)     5.42  
  ( 4.21 to 7.43 )  
  5.55  
  ( 4.27 to 6.74 )  
  4.01  
  ( 3.94 to 5.59 )  
irDoR (irRC) SCLC cohort (n=43, 42, 45)     5.95  
  ( 4.53 to 10.8 )  
  5.78  
  ( 4.44 to 6.67 )  
  4.21  
  ( 3.91 to 6.41 )  
DoR (mWHO criteria) SCLC cohort (n=43, 42, 45)     7.62  
  ( 4.90 to 11.1 )  
  5.78  
  ( 3.94 to 6.57 )  
  4.21  
  ( 3.91 to 5.95 )  

No statistical analysis provided for Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC



8.  Secondary:   Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade   [ Time Frame: Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose) ]

Measure Type Secondary
Measure Title Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade
Measure Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who received at least 1 dose of blinded active or placebo ipilimumab with or without paclitaxel/carboplatin. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  71     67     65  
Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade  
[units: Participants]
     
Deaths (total)     52     50     51  
Deaths within 30 days of last dose of study drug     11     7     8  
Deaths within 70 days of last dose of study drug     21     16     18  
SAEs (total)     49     36     33  
SAEs, Grade 3     17     16     9  
SAEs, Grade 4     10     4     5  
SAEs, Grade 5     20     15     18  
SAEs, Drug-related     20     13     11  
SAEs, Drug-related Grade 5     2     1     2  
AEs leading to discontinuation (disc) (total)     28     19     15  
AEs leading to disc, Drug-related (all)     16     7     8  
AEs leading to disc, Drug-related Grade 3     9     6     4  
AEs leading to disc, Drug-related Grade 4     1     0     0  
AEs leading to disc, Drug-related Grade 5     1     0     1  
AEs (total)     71     64     64  
AEs, Grades 3 and 4     40     36     26  
AEs, Drug-related Any Grade     56     56     54  
AEs, Drug-related Grades 3 and 4     29     26     24  
AEs, Drug-related Grade 5     2     1     2  

No statistical analysis provided for Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade



9.  Secondary:   Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade   [ Time Frame: At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent ]

Measure Type Secondary
Measure Title Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
Measure Description CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.
Time Frame At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study hematology test result available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  71     67     65  
Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade  
[units: Percentage of participants]
     
White blood cell count, Grades 3 and 4     7.7     6.2     3.2  
Hemoglobin, Any grade     90.8     98.5     90.2  
Hemoglobin, Grades 3 and 4     10.8     6.2     6.3  
ANC, Grades 3 and 4     7.7     1.5     9.5  
Platelets, Grades 3 and 4     1.5     3.1     9.5  

No statistical analysis provided for Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade



10.  Secondary:   irPFS in Participants With SCLC Per irRC   [ Time Frame: Randomization date to date of irPD or death (maximum reached: 22 months) ]

Measure Type Secondary
Measure Title irPFS in Participants With SCLC Per irRC
Measure Description IRC performed TA.
Time Frame Randomization date to date of irPD or death (maximum reached: 22 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  43     42     45  
irPFS in Participants With SCLC Per irRC  
[units: Months]
Mean ( 95% Confidence Interval )
  5.68  
  ( 5.19 to 6.87 )  
  6.44  
  ( 5.29 to 7.75 )  
  5.26  
  ( 4.67 to 5.72 )  


Statistical Analysis 1 for irPFS in Participants With SCLC Per irRC
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.1098
Hazard Ratio (HR) [4] 0.751
95% Confidence Interval ( 0.475 to 1.188 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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Statistical Analysis 2 for irPFS in Participants With SCLC Per irRC
Groups [1] Ipilimumab + Paclitaxel/Carboplatin (Sequential) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided log rank
P Value [3] 0.0282
Hazard Ratio (HR) [4] 0.640
95% Confidence Interval ( 0.403 to 1.1016 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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11.  Secondary:   Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade   [ Time Frame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent ]

Measure Type Secondary
Measure Title Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade
Measure Description ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.
Time Frame At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study liver function measurement available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  65     65     62  
Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade  
[units: Participants]
     
Alanine aminotransferase (ALT), Grade 1     24     15     19  
ALT, Grade 2     2     4     3  
ALT, Grades 3 and 4     1     1     1  
Aspartate aminotransferase (AST), Grade 1     16     18     20  
AST, Grade 2     0     2     0  
AST, Grades 3 and 4     1     1     1  
Total bilirubin, Grade 1     1     3     2  
Total bilirubin, Grade 2     3     2     1  
Total bilirubin, Grades 3 and 4     0     0     0  
Alkaline phosphatase, Grade 1     24     28     24  
Alkaline phosphatase, Grade 2     1     2     3  
Alkaline phosphatase, Grades 3 and 4     0     1     1  

No statistical analysis provided for Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade



12.  Secondary:   Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings   [ Time Frame: At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent ]

Measure Type Secondary
Measure Title Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
Measure Description Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.
Time Frame At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study measurement available.One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  71     67     65  
Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings  
[units: Participants]
     
Vital sign measurements     0     0     0  
Physical examination findings     0     0     0  

No statistical analysis provided for Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings



13.  Secondary:   Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade   [ Time Frame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment ]

Measure Type Secondary
Measure Title Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade
Measure Description ULN=upper limit of normal. Lipase (U/L) Gr 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Creatine (mg/dL) Grade 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.
Time Frame At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study pancreatic enzyme laboratory test measurement available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  71     67     65  
Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade  
[units: Percentage of participants]
     
Lipase, Grades 3 and 4     7.7     6.2     3.2  
Amylase, Grades 3 and 4     1.5     4.6     1.6  

No statistical analysis provided for Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade



14.  Secondary:   Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline   [ Time Frame: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment ]

Measure Type Secondary
Measure Title Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline
Measure Description An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.
Time Frame Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with at least 1 HAHA measurement prior to and at least 1 after the first ipilimumab dose and with an increase in HAHA measurement from baseline.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)  
Number of Participants Analyzed  
[units: participants]
  61     56  
Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline  
[units: Participants]
  2     1  

No statistical analysis provided for Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline



15.  Secondary:   Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade   [ Time Frame: Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose) ]

Measure Type Secondary
Measure Title Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade
Measure Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who received at least 1 dose of blinded active or placebo ipilimumab with or without paclitaxel/carboplatin.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  42     42     44  
Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade  
[units: Participants]
     
Deaths (total)     37     31     35  
Deaths within 30 days of last dose of study drug     6     2     1  
Deaths within 70 days of last dose of study drug     13     7     8  
SAEs (total)     25     21     20  
SAEs, Grade 3     7     6     4  
SAEs, Grade 4     3     4     4  
SAEs, Grade 5     12     7     7  
SAEs, Drug-related     10     12     6  
SAEs, Drug-related Grade 5     1     0     0  
AEs leading to discontinuation (disc) (total)     14     13     12  
AEs leading to disc, Drug-related (all)     9     7     7  
AEs leading to disc, Drug-related Grade 3     3     3     4  
AEs leading to disc, Drug-related Grade 4     2     2     0  
AEs leading to disc, Drug-related Grade 5     1     0     0  
AEs (total)     41     40     43  
AEs, Grades 3 and 4     19     22     19  
AEs, Grade 5     12     7     7  
AEs, Drug-related (all)     36     40     40  
AEs, Drug-related,Grades 3 and 4     18     21     13  
AEs, Drug-related, Grade 5     1     0     0  

No statistical analysis provided for Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade



16.  Secondary:   Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade   [ Time Frame: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment ]

Measure Type Secondary
Measure Title Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
Measure Description CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Gr 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.
Time Frame At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study hematology test result available.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  42     42     44  
Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade  
[units: Participants]
     
White blood cells, Grade 1 (n=39, 42, 43)     7     11     13  
White blood cells, Grade 2 (n= 39, 42, 43)     10     9     7  
White blood cells, Grades 3 (n= 39, 42, 43)     0     2     0  
White blood cells, Grade 4 (n= 39, 42, 43)     0     0     0  
Absolute neutrophil count, Grade 1 (n= 39, 42, 43)     8     8     8  
Absolute neutrophil count, Grade 2 (n= 39, 42, 43)     8     9     91  
Absolute neutrophil count, Grade 3 (n= 39, 42, 43)     2     2     1  
Absolute neutrophil count, Grade 4 (n= 39, 42, 43)     1     2     0  
Platelet count, Grade 1 (n= 39, 42, 43)     15     18     23  
Platelet count, Grade 2 (n= 39, 42, 43)     2     3     3  
Platelet count, Grade 3 (n= 39, 42, 43)     1     2     1  
Platelet count, Grade 4 (n= 39, 42, 43)     0     1     0  
Hemoglobin, Grade 1 (n= 39, 42, 43)     26     24     25  
Hemoglobin, Grade 2 (n= 39, 42, 43)     8     10     11  
Hemoglobin, Grade 3 (n= 39, 42, 43)     2     2     3  
Hemoglobin, Grade 4 (n= 39, 42, 43)     0     2     0  

No statistical analysis provided for Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade



17.  Secondary:   Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade   [ Time Frame: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment ]

Measure Type Secondary
Measure Title Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade
Measure Description ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. ULN=Upper limit of normal among all laboratory ranges. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.
Time Frame At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study liver function test result available.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  42     42     44  
Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade  
[units: Participants]
     
ALT, Grade 1     12     12     8  
ALT, Grade 2     2     3     1  
ALT, Grades 3 & 4     7     2     0  
AST, Grade 1     11     13     12  
AST, Grade 2     4     1     2  
AST, Grades 3 & 4     5     3     0  
Total bilirubin, Grade 1     4     5     3  
Total bilirubin, Grade 2     1     0     0  
Total bilirubin, Grades 3 & 4     1     0     0  
ALK, Grade 1     15     14     16  
ALK, Grade 2     1     3     2  
ALK, Grades 3 & 4     0     0     0  

No statistical analysis provided for Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade



18.  Secondary:   Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade   [ Time Frame: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment ]

Measure Type Secondary
Measure Title Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade
Measure Description ULN=upper limit of normal. Lipase (U/L) Grade (Gr) 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Gr 2 >1.5 to 2.0*ULN, Gr 3 >2.0 to 5.0*ULN, Gr 4 >5.0*ULN. Creatine (mg/dL) Gr 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.
Time Frame At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study pancreatic enzyme or other laboratory test measurement available.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (concurrent). The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes every 3 weeks as part of induction. Participants could also receive additional maintenance ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (sequential). The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes every 3 weeks as part of induction. Participants could also receive additional maintenance ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  42     42     44  
Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade  
[units: Percentage of participants]
     
Lipase, Grades 3 and 4     7.7     16.7     11.6  
Amylase, Grades 3 and 4     5.1     4.8     4.7  
Creatinine, Grades 3 and 4     0     0     0  

No statistical analysis provided for Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade



19.  Secondary:   Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria   [ Time Frame: Randomization date to date of progression or death (of censored, maximum reached: 22 months) ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
Measure Description By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment.
Time Frame Randomization date to date of progression or death (of censored, maximum reached: 22 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  43     42     45  
Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria  
[units: Months]
Mean ( 95% Confidence Interval )
  3.89  
  ( 2.89 to 5.85 )  
  5.22  
  ( 4.14 to 6.57 )  
  5.19  
  ( 4.40 to 5.59 )  


Statistical Analysis 1 for Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided Log Rank
P Value [3] 0.3846
Hazard Ratio (HR) [4] 0.933
95% Confidence Interval ( 0.588 to 1.481 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
Groups [1] Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided Log Rank
P Value [3] 0.3700
Hazard Ratio (HR) [4] 0.927
95% Confidence Interval ( 0.591 to 1.453 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



20.  Secondary:   Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings   [ Time Frame: Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment ]

Measure Type Secondary
Measure Title Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
Measure Description Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.
Time Frame Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study measurement available.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  42     42     44  
Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings  
[units: Participants]
     
Vital sign measurements     0     0     0  
Physical examination findings     0     0     0  

No statistical analysis provided for Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings



21.  Secondary:   Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline   [ Time Frame: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment ]

Measure Type Secondary
Measure Title Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline
Measure Description An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.
Time Frame Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with SCLC who had at least 1 HAHA measurement prior to and at least 1 after the first ipilimumab dose and with an increase in HAHA measurement from baseline.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Ipilimumab + Paclitaxel/Carboplatin (Sequential)  
Number of Participants Analyzed  
[units: participants]
  38     41  
Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline  
[units: Participants]
   
Positive at any timepoint (n=42, 42)     2     3  
Positive postbaseline (n=38, 41)     2     0  

No statistical analysis provided for Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline



22.  Secondary:   Overall Survival in Participants With SCLC   [ Time Frame: Randomization date to date of death (of censored, maximum reached: 22 months) ]

Measure Type Secondary
Measure Title Overall Survival in Participants With SCLC
Measure Description Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.
Time Frame Randomization date to date of death (of censored, maximum reached: 22 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants with SCLC who were randomized to a treatment group.

Reporting Groups
  Description
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Placebo + Paclitaxel/Carboplatin During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.

Measured Values
    Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)     Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)     Placebo + Paclitaxel/Carboplatin  
Number of Participants Analyzed  
[units: participants]
  43     42     45  
Overall Survival in Participants With SCLC  
[units: Months]
Median ( 95% Confidence Interval )
  3.89  
  ( 2.89 to 5.85 )  
  5.22  
  ( 4.14 to 6.57 )  
  5.19  
  ( 4.40 to 5.59 )  


Statistical Analysis 1 for Overall Survival in Participants With SCLC
Groups [1] Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) vs. Placebo + Paclitaxel/Carboplatin
Method [2] 1-sided Log Rank
P Value [3] 0.4132
Hazard Ratio (HR) [4] 0.947
95% Confidence Interval ( 0.585 to 1.536 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Overall Survival in Participants With SCLC
Groups [1] All groups
Method [2] 1-sided Log Rank
P Value [3] 0.1287
Hazard Ratio (HR) [4] 0,753
95% Confidence Interval ( 0.461 to 1.232 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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