Clinical Trial Results:
A Phase 1/2 Pharmacokinetic Multi-tumor Study of Subcutaneous Formulation of Ipilimumab Monotherapy and in Combination with Subcutaneous Nivolumab
Summary
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EudraCT number |
2019-004380-40 |
Trial protocol |
GB IT |
Global end of trial date |
18 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jan 2024
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First version publication date |
06 Jan 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CA209-76U
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04311710 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Apr 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Jan 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of this trial is to evaluate the PK, safety, and tolerability of high concentrations of ipilimumab administered subcutaneously with and without rHuPH20 as monotherapy and in combination with SC nivolumab with rHuPH20 in participants with one of the following advanced or metastatic tumor types: melanoma, HCC, mUC, NSCLC, and RCC.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jun 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 14
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Country: Number of subjects enrolled |
New Zealand: 1
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Country: Number of subjects enrolled |
United States: 6
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Worldwide total number of subjects |
21
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EEA total number of subjects |
14
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
Pre-assignment
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Screening details |
21 participants were treated. | ||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Arm title
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Part 1 Arm A | ||||||||||||||||||
Arm description |
4 mg/kg ipilimumab (BMS-734016) + rHuPH20 administered subcutaneously every 3 weeks X 1 cycle (one cycle is 21 days) followed by 3 mg/kg ipilimumab + 1 mg/kg nivolumab (BMS-936558) administered intravenously every 3 weeks X 3 cycles followed by 480 mg nivolumab administered intravenously every 4 weeks for up to 104 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
BMS-734016 + BMS-936558
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
3 mg/kg (BMS-734016) + 1 mg/kg (BMS-936558) Q3W x 3 cycles
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Investigational medicinal product name |
BMS-936558
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
480 mg monotherapy Q4W until completion for 104 weeks
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Investigational medicinal product name |
BMS-734016+ rHuPH20
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
4 mg/kg Q3W x 1 cycle
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Baseline characteristics reporting groups
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Reporting group title |
Part 1 Arm A
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Reporting group description |
4 mg/kg ipilimumab (BMS-734016) + rHuPH20 administered subcutaneously every 3 weeks X 1 cycle (one cycle is 21 days) followed by 3 mg/kg ipilimumab + 1 mg/kg nivolumab (BMS-936558) administered intravenously every 3 weeks X 3 cycles followed by 480 mg nivolumab administered intravenously every 4 weeks for up to 104 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part 1 Arm A
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Reporting group description |
4 mg/kg ipilimumab (BMS-734016) + rHuPH20 administered subcutaneously every 3 weeks X 1 cycle (one cycle is 21 days) followed by 3 mg/kg ipilimumab + 1 mg/kg nivolumab (BMS-936558) administered intravenously every 3 weeks X 3 cycles followed by 480 mg nivolumab administered intravenously every 4 weeks for up to 104 weeks. |
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End point title |
AUC (0-21d) of ipilimumab [1] | ||||||||
End point description |
Area under the concentration-time curve from time 0 to 21 days postdose
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End point type |
Primary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24, 48, 72, 168, 336 hours post-dose. End-of-infusion on Cycle 2 Day 1 (Cycle 1 = 3 weeks)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Cmax [2] | ||||||||
End point description |
Maximum observed serum concentration of ipilimumab
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End point type |
Primary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24, 48, 72, 168, 336 hours post-dose. End-of-infusion on Cycle 2 Day 1 (Cycle 1 = 3 weeks)
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Cavg21d [3] | ||||||||
End point description |
Average concentration of ipilimumab during 21 days post-first dose
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End point type |
Primary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24, 48, 72, 168, 336 hours post-dose. End-of-infusion on Cycle 2 Day 1 (Cycle 1 = 3 weeks)
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
C21d [4] | ||||||||
End point description |
Observed concentration of ipilimumab at 21 days postdose
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End point type |
Primary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24, 48, 72, 168, 336 hours post-dose. End-of-infusion on Cycle 2 Day 1 (Cycle 1 = 3 weeks)
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Time of Maximum Observed Concentration (Tmax) of Ipilimumab [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24, 48, 72, 168, 336 hours post-dose. End-of-infusion on Cycle 2 Day 1 (Cycle 1 = 3 weeks)
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants with Adverse Events (AEs) | ||||||||
End point description |
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
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End point type |
Secondary
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End point timeframe |
From first dose up to 30 days post last dose (up to approximately 25 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Serious AEs (SAEs) | ||||||||
End point description |
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose:
-Results in death
-Is life-threatening
-Requires inpatient hospitalization or causes prolongation of existing hospitalization
-Results in persistent or significant disability/incapacity
-Is a congenital anomaly/birth defect
-Is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes listed in the definition above.)
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End point type |
Secondary
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End point timeframe |
From first dose up to 100 days post last dose (up to approximately 27 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Laboratory Abnormalities | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of participants experiencing laboratory test abnormalities. Laboratory analysis was performed on the following: hematology, liver and kidney function, and other chemistry testing.
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End point type |
Secondary
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End point timeframe |
From first dose up to 30 days post last dose (up to approximately 25 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants who Died During the Study | ||||||
End point description |
Number of participants who died
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End point type |
Secondary
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End point timeframe |
From first dose up to 100 days post last dose (up to approximately 27 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Adverse Events (AEs) Leading to Discontinuation | ||||||||
End point description |
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
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End point type |
Secondary
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End point timeframe |
From first dose up to 30 days post last dose (up to approximately 25 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Anaphylactic, Hypersensitivity, Injection, and Infusion Reactions | ||||||||||||||
End point description |
The number of participants with AEs in the broad standardized MedDRA query (SMQ) of Anaphylactic Reaction and the select AE hypersensitivity/ injection/infusion reaction category.
MedDRA = Medical Dictionary for Regulatory Activities
SMQ = standardized MedDRA queries
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End point type |
Secondary
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End point timeframe |
From first dose up to 2 days after study drug administration (up to approximately 24 months)
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No statistical analyses for this end point |
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End point title |
Number of Participants who Develop Anti-ipilimumab Antibodies | ||||||||||
End point description |
-ADA (anti-drug antibody)-positive: A subject with at least one ADA-positive sample relative to baseline (ADA-negative at baseline or ADA titer to be at least 4-fold or greater (≥) than baseline positive titer at any time after initiation of treatment)
-Neutralizing Positive: At least one ADA-positive sample with neutralizing antibodies detected post-baseline
-ADA-negative: A participant with no ADA-positive sample after initiation of treatment
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End point type |
Secondary
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End point timeframe |
Day 1 Cycle 1 pre-dose, 24 hours post-dose, and Day 1 pre-dose of Cycles 2-6 (Cycle 1-4 = 3 weeks each and cycle 5-26 = 4 weeks each)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Anti-nivolumab Antibodies | ||||||||||||
End point description |
-ADA (anti-drug antibody)-positive: A subject with at least one ADA-positive sample relative to baseline (ADA-negative at baseline or ADA titer to be at least 4-fold or greater (≥) than baseline positive titer at any time after initiation of treatment)
-Neutralizing Positive: At least one ADA-positive sample with neutralizing antibodies detected post-baseline
-ADA-negative: A participant with no ADA-positive sample after initiation of treatment
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End point type |
Secondary
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End point timeframe |
Day 1 pre-dose of Cycles 2-6, 10, 14, 18, 22, and 26 (Cycle 1-4 = 3 weeks each and cycle 5-26 = 4 weeks each)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All-cause mortality was assessed from first dose to study completion (up to approximately 30 months) SAEs and NSAEs were assessed from first dose to 100 days following last dose (up to approximately 27 months)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
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Reporting groups
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Reporting group title |
PART 1 ARM A
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Reporting group description |
4 mg/kg ipilimumab (BMS-734016) + rHuPH20 administered subcutaneously every 3 weeks X 1 cycle (one cycle is 21 days) followed by 3 mg/kg ipilimumab + 1 mg/kg nivolumab (BMS-936558) administered intravenously every 3 weeks X 3 cycles followed by 480 mg nivolumab administered intravenously every 4 weeks for up to 104 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |