Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies (MDX1106-01)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00441337
First received: February 27, 2007
Last updated: February 5, 2015
Last verified: February 2015
Results First Received: January 21, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Carcinoma, Non-Small-Cell Lung
Colorectal Cancer
Malignant Melanoma
Renal Cancer
Prostate Cancer
Intervention: Biological: MDX-1106

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study from 25 October 2006 to 27 November 2009. After completion of a single dose (cycle 1), those meeting criteria could be re-treated with 2 additional doses (cycle 2); and additional cycles. Participants who had a complete response (CR) or partial response (PR) at end of re-treatment were followed-up until disease progression for 2 years.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
39 participants were enrolled and 39 were treated with at least 1 dose or a partial dose of study drug.

Reporting Groups
  Description
0.3 mg/kg Nivolumab 0.3 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.

Participant Flow:   Overall Study
    0.3 mg/kg Nivolumab     1 mg/kg Nivolumab     3 mg/kg Nivolumab     10 mg/kg Nivolumab  
STARTED     6     6     6     21  
COMPLETED     0     0     0     0  
NOT COMPLETED     6     6     6     21  
Disease Progression                 6                 6                 4                 18  
Lost to Follow-up                 0                 0                 0                 1  
Sponsor Decision                 0                 0                 1                 2  
Did not meet inclusion criteria                 0                 0                 1                 0  



  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.
All participants who received at least 1 dose or any partial dose of study drug.

Reporting Groups
  Description
0.3 mg/kg Nivolumab 0.3 mg of nivolumab per kg of body weight (mg/kg) was administered in a single IV infusion on Day 1 with 10% of the dose infused over 6 minutes and after a 1 hour observation period, the balance was administered over 60 minutes. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
1 mg/kg Nivolumab 1 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
3 mg/kg Nivolumab 3 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
10 mg/kg Nivolumab 10 mg of nivolumab per kg of body weight was administered in a single IV infusion over 60 minutes on Day 1. Eligible participants could be re-treated and receive 2 more doses (1 dose every 4 weeks) at same dose as the single dose if: disease was stable, no drug intolerance was observed, no complete response (CR) or partial response (PR) was observed, or they had a positive immunogenicity sample within 4 weeks prior to re-treatment. Those who responded to therapy with a CR or PR were eligible for long-term follow-up until either progressive disease (PD) or 2 years elapsed.
Total Total of all reporting groups

Baseline Measures
    0.3 mg/kg Nivolumab     1 mg/kg Nivolumab     3 mg/kg Nivolumab     10 mg/kg Nivolumab     Total  
Number of Participants  
[units: participants]
  6     6     6     21     39  
Age  
[units: years]
Mean ± Standard Deviation
  56.5  ± 5.7     68.3  ± 9.4     61.0  ± 10.4     63.2  ± 10.0     62.6  ± 9.7  
Gender  
[units: participants]
         
Female     2     3     2     10     17  
Male     4     3     4     11     22  
Race/Ethnicity, Customized  
[units: participants]
         
White     4     3     4     18     29  
Black     2     3     2     3     10  
Region of Enrollment  
[units: participants]
         
United States     6     6     6     21     39  
Body Weight in kilograms (kg)  
[units: kg]
Median ( Full Range )
  96.8  
  ( 88 to 136 )  
  73.9  
  ( 62 to 80 )  
  81.9  
  ( 55 to 98 )  
  81.3  
  ( 56 to 118 )  
  81.3  
  ( 55 to 136 )  
Time since initial diagnosis (years)  
[units: Years]
Median ( Full Range )
  3.7  
  ( 1.4 to 6.8 )  
  2.7  
  ( 1.5 to 14.0 )  
  5.6  
  ( 0.7 to 11.4 )  
  4.1  
  ( 1.0 to 19.8 )  
  3.8  
  ( 0.7 to 19.8 )  
Type of Malignancy  
[units: participants]
         
Prostate Cancer     0     1     2     5     8  
Melanoma     0     2     0     8     10  
Non-small cell lung cancer     1     1     2     2     6  
Renal cell cancer     0     0     0     1     1  
Colorectal cancer     5     2     2     5     14  
Stage of Malignancy at Screening Diagnosis [1]
[units: participants]
         
Stage I     0     0     0     0     0  
Stage II     0     0     0     0     0  
Stage III     1     0     0     0     1  
Stage IV     5     6     6     21     38  
[1] The investigator reported the screening malignancy stage for each type of cancer using the American Joint Committee on Cancer Classification (Stages I, II, III, and IV).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population   [ Time Frame: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation ]

2.  Primary:   Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

3.  Primary:   Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

4.  Primary:   Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

5.  Primary:   Mean Elimination Half-life (T-HALF) Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

6.  Primary:   Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

7.  Primary:   Mean Volume of Distribution (Vz) Post-Single Dose   [ Time Frame: Day 1 to Day 85 ]

8.  Primary:   Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population   [ Time Frame: Day 1 up to 2 Years. ]

9.  Primary:   Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC)   [ Time Frame: Day 1 to Day 85 ]

10.  Secondary:   Number of Participants With Best Overall Response (BOR) by Category in Safety Population   [ Time Frame: Day 1 to Day 85 ]

11.  Secondary:   Percentage of Participants With Disease Control and Major Durable Disease Control   [ Time Frame: Day 1 to 2 Years ]

12.  Secondary:   Median Time to Tumor Response and Duration of Tumor Response   [ Time Frame: Day 1 to 2 Years ]

13.  Secondary:   Time to Tumor Progression and Tumor Progression Free Survival   [ Time Frame: Day 1 to 2 Years ]

14.  Secondary:   Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population   [ Time Frame: Day 1 to 2 Years ]

15.  Secondary:   Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population   [ Time Frame: Day 29, Day 57, Day 85 ]

16.  Secondary:   Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population   [ Time Frame: Baseline, Day 2, Day 85, Day 113 ]

17.  Secondary:   Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population   [ Time Frame: Baseline, Day 1 ]

18.  Secondary:   Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population   [ Time Frame: Baseline, Day 1 ]

19.  Secondary:   Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population   [ Time Frame: Baseline, Day 1 ]

20.  Secondary:   Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population   [ Time Frame: Baseline, Day 1 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00441337     History of Changes
Other Study ID Numbers: CA209-001 ST, MDX1106-01
Study First Received: February 27, 2007
Results First Received: January 21, 2015
Last Updated: February 5, 2015
Health Authority: United States: Food and Drug Administration