A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00730639
First received: August 4, 2008
Last updated: March 24, 2016
Last verified: March 2016
Results First Received: February 22, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Metastatic Castration-resistant Prostrate Cancer (mCRPC)
Renal Cell Carcinoma (RCC)
Metastatic Melanoma (MEL)
Non-small Cell Lung Cancer (NSCLC)
Intervention: Biological: BMS-936558 (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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
395 participants were enrolled and 306 were treated. 89 were not treated because they failed to meet study eligibility criteria or died prior to the initiation of treatment. All participants had received at least 1 prior cancer therapy. Study is on-going.

Reporting Groups
  Description
0.1 mg/kg Nivolumab 0.1 milligrams (mg) of nivolumab per kilogram (kg) of body weight (mg/kg)was administered intravenously (IV) every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed complete response (CR), worsening progressive disease (PD), or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, partial response (PR), or stable disease (SD), who subsequently experienced confirmed PD.
0.3 mg/kg Nivolumab 0.3 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
1.0 mg/kg Nivolumab 1.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
3.0 mg/kg Nivolumab 3.0 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.
10 mg/kg Nivolumab 10 mg/kg nivolumab was administered by IV every 2 weeks; Dosing on Days 1, 15, 29, and 43 (Cycle 1). Response was assessed between Days 52 and 56, before the first dose of the next cycle. Participants were treated until confirmed CR, worsening PD, or unacceptable toxicity, up to 12 Cycles of treatment (96 weeks; 48 doses). Follow-up was up to 48 weeks. Re-initiation of study therapy was permitted for participants who entered the follow-up period with ongoing CR, PR, or SD, who subsequently experienced confirmed PD.

Participant Flow:   Overall Study
    0.1 mg/kg Nivolumab     0.3 mg/kg Nivolumab     1.0 mg/kg Nivolumab     3.0 mg/kg Nivolumab     10 mg/kg Nivolumab  
STARTED     17     18     86     54     131  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     17     18     86     54     131  
Adverse Event                 3                 0                 9                 8                 23  
Complete Response                 0                 0                 2                 2                 1  
Completed Maximum Cycles                 0                 0                 11                 3                 6  
Death                 0                 0                 0                 0                 2  
Disease Progression                 12                 13                 48                 32                 88  
non-specified                 0                 0                 4                 2                 3  
Protocol Violation                 0                 0                 1                 0                 0  
Withdrawal by Subject                 0                 0                 6                 3                 4  
Treatment on-going                 2                 5                 5                 4                 4  



  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 treated participants.

Reporting Groups
  Description
0.1 mg/kg Nivolumab Intravenous (IV) solution of 0.1 milligram nivolumab per kilogram of body weight (mg/kg) was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
0.3 mg/kg Nivolumab 0.3 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
1.0 mg/kg Nivolumab 1.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
3.0 mg/kg Nivolumab 3.0 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
10 mg/kg Nivolumab 10 mg/kg nivolumab was administered every 2 weeks; Dosing on Days 1, 15, 29, and 43 of each treatment cycle.
Total Total of all reporting groups

Baseline Measures
    0.1 mg/kg Nivolumab     0.3 mg/kg Nivolumab     1.0 mg/kg Nivolumab     3.0 mg/kg Nivolumab     10 mg/kg Nivolumab     Total  
Number of Participants  
[units: participants]
  17     18     86     54     131     306  
Age  
[units: years]
Mean (Full Range)
  57.5  
  (33 to 79)  
  60.8  
  (29 to 85)  
  61.8  
  (37 to 83)  
  62.7  
  (32 to 81)  
  63.1  
  (30 to 85)  
  62.2  
  (29 to 85)  
Age, Customized  
[units: participants]
           
Less than (<) 65 years     13     9     49     30     67     168  
Greater than or equal to (>)= 65 years     4     9     37     24     64     138  
Gender  
[units: participants]
           
Female     4     9     26     21     43     103  
Male     13     9     60     33     88     203  
Tumor Type  
[units: participants]
           
Squamous Non-Small Cell Lung Cancer (SQ NSCLC)     0     0     15     18     21     54  
Non-Squamous NSCLC (NSQ NSCLC)     0     0     18     19     37     74  
Melanoma     17     18     35     17     20     107  
Renal Cell Carcinoma (RCC)     0     0     18     0     16     34  
Castrate-Resistant Prostate Cancer (CRC)     0     0     0     0     19     19  
MCRPC     0     0     0     0     17     17  
NSCLC of Unspecified Histology     0     0     0     0     1     1  



  Outcome Measures
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1.  Primary:   Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs   [ Time Frame: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years ]

2.  Primary:   Number of Participants With Abnormal Serum Chemistry Laboratory Values   [ Time Frame: Day 1 up to June 2013, approximately 4 years ]

3.  Primary:   Number of Participants With Abnormal Hematology Laboratory Values   [ Time Frame: Day 1 up to June 2013, approximately 4 years ]

4.  Secondary:   Immunogenicity Assessment   [ Time Frame: Day 1 up to June 2013, approximately 4 years ]

5.  Secondary:   Objective Response Rate   [ Time Frame: Day 1 up to June 2013, approximately 4 years ]

6.  Secondary:   Duration of Tumor Response   [ Time Frame: Day 1 up to June 2013, approximately 4 years ]

7.  Secondary:   Geometric Mean Maximum Serum Concentration (Cmax)   [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]

8.  Secondary:   Median Time of Maximum Serum Concentration (Tmax)   [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]

9.  Secondary:   Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose   [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]

10.  Secondary:   Geometric Mean Total Body Clearance of Drug From Serum (CLT)   [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3 ]

11.  Secondary:   Mean Effective Half-life (T-HALFeff)   [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3 ]


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00730639     History of Changes
Other Study ID Numbers: CA209-003
MDX1106-03 ( Other Identifier: BMS )
Study First Received: August 4, 2008
Results First Received: February 22, 2016
Last Updated: March 24, 2016
Health Authority: United States: Food and Drug Administration