Phase I Biomarker Study (BMS-936558)
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01358721
Collaborator
Ono Pharma USA Inc (Industry)
119
14
4
91.9
8.5
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacodynamic and biologic properties of BMS-936558 in subjects with metastatic renal cell carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Intervention Model: Parallel Dose Comparison
Study Design
Study Type:
Interventional
Actual Enrollment
:
119 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
An Exploratory Study to Investigate the Immunomodulatory Activity of Various Dose Levels of Anti Programmed-Death-1 (PD-1) Antibody (BMS-936558) in Subjects With Metastatic Clear Cell Renal Cell Carcinoma (RCC).
Actual Study Start Date
:
Sep 23, 2011
Actual Primary Completion Date
:
Dec 1, 2014
Actual Study Completion Date
:
May 22, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1: BMS-936558
|
Drug: BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 0.3 mg/kg, Every 3 weeks, Indefinitely depending on response
|
| Experimental: Arm 2: BMS-936558
|
Drug: BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 2 mg/kg, Every 3 weeks, Indefinitely depending on response
|
| Experimental: Arm 3: BMS-936558
|
Drug: BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 10 mg/kg, Every 3 weeks, Indefinitely depending on response
|
| Experimental: Arm 4: BMS-936558 (treatment naive) |
Drug: BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 10 mg/kg, Every 3 weeks, Indefinitely depending on response
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Activated and Memory T Cells [Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1]
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC)
- Mean Serum Cytokines: CXCL9 [Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)]
Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)
- Mean Serum Cytokines CXCL10 (IP10) [Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months)]
Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)
- Mean CD4 T Cell Infiltration [Cycle 2 Day 8 168 Hr post dose]
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD4 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).
- Mean CD8 T Cell Infiltration [168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection)]
The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD8 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC).
Secondary Outcome Measures
- Best Overall Response in the BMS-936558 Arms [Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months)]
Baseline and post-nivolumab treatment modulation of serum levels of interferon-gamma stimulated chemokines CXCL9 and CXCL10 (IP10) were assessed. The participant's best response designation over the study as a whole, recorded between the date of first study drug administration and the date of objectively documented progression per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
- Progression Free Survival Rate in BMS-936558 [Progression free survival rate will be assessed in each individual treatment arm by tumor assessments at 16, 24, and 48 weeks. From initial dose to end of study (assessed up to 39 months)]
PFS is defined as the time from treatment arm assignment to the date of first documented disease progression. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have any on study tumor assessments will be censored on the date they were assigned a treatment arm. PFS rate is the percentage of participants who did not have disease progression at particular time points (16 weeks, 24 weeks, 48 weeks)
- Objective Response Rate in BMS-936558 [Up to 22 months after study start]
The total number of subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) divided by the total number of participants in the population of interest, and expressed as a percentage.
- Duration of Objective Response for BMS-936558 [The time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death (assessed up to 39 months)]
The duration of response is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. For subjects who neither progress nor die, the duration of response will be censored at the date of their last tumor assessment.
- Duration of Stable Disease for BMS-936558 as Measured in Participants Whose Best Overall Response is Stable Disease as the Time From Baseline Until the Date of Documented Disease Progression or Death [The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months)]
Duration of stable disease (SD) is defined in participants whose BOR is SD at the time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first). Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment
- Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558 [Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.]
Blood samples to evaluate the development of a positive anti-drug antibodies (ADA) response at the doses tested will be collected at time-points pre-dose, C4D1, C8D1 and during follow-up.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
-
Women and men ≥ 18 years of age.
-
Histologic confirmation of renal cell carcinoma with a clear cell component.
-
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
-
Tumor sites that can be accessed for repeat biopsies at acceptable clinical risk.
-
Previously treated subjects must have failed at least 1 prior anti-angiogenic agent and can have a maximum of 3 prior systemic treatments for renal cell cancer.
-
Subjects in the treatment naive arm cannot have received prior systemic therapy for their renal cell carcinoma.
Exclusion Criteria:
-
Active or progressing brain metastases.
-
Active concomitant.
-
Active or history of autoimmune disease.
-
Active use of systemic corticosteroids.
-
Prior therapy with Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4), anti Programmed death-1 (anti-PD1), anti Programmed death ligand 1 (anti-PD-L1), anti Programmed death ligand 2 (anti-PD-L2), anti-CD137, anti-CD40, anti-OX40 antibodies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ucsf Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94115 |
| 2 | Yale University School Of Medicine | New Haven | Connecticut | United States | 06520 |
| 3 | H. Lee Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 4 | University Of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 5 | The Bunting-Blaustein Cancer Research Building | Baltimore | Maryland | United States | 21231 |
| 6 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 7 | Dana Farber Cancer Inst | Boston | Massachusetts | United States | 02215 |
| 8 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 9 | Providence Portland Med Ctr | Portland | Oregon | United States | 97213 |
| 10 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
| 11 | Upmc Cancer Pavilion | Pittsburgh | Pennsylvania | United States | 15232 |
| 12 | University Of Wisconsin Carbone Cancer Center | Madison | Wisconsin | United States | 53705 |
| 13 | Local Institution | Villejuif Cedex | France | 94805 | |
| 14 | Local Institution | Pamplona | Spain | 31192 |
Sponsors and Collaborators
- Bristol-Myers Squibb
- Ono Pharma USA Inc
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- BMS Clinical Trial Information
- BMS Clinical Trial Patient Recruiting
- Investigator Inquiry Form
- FDA Safety Alerts and Recalls
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01358721
Other Study ID Numbers:
- CA209-009
- 2011-005379-18
First Posted:
May 24, 2011
Last Update Posted:
Oct 28, 2021
Last Verified:
Oct 1, 2021
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 119 participants were enrolled, 92 participants were randomized of whom 1 was randomized but not treated. 27 participants did not enter treatment period due to: Participant withdrawal n = 1, Death n = 1, No longer meets criteria n = 22, Other reasons n = 3 |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Period Title: Overall Study | ||||
| STARTED | 22 | 22 | 23 | 24 |
| COMPLETED | 1 | 0 | 1 | 0 |
| NOT COMPLETED | 21 | 22 | 22 | 24 |
Baseline Characteristics
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Total of all reporting groups |
| Overall Participants | 22 | 22 | 23 | 24 | 91 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
61.0
(.41)
|
60.8
(9.89)
|
57.7
(10.98)
|
61.8
(10.3)
|
60.3
(10.13)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
13.6%
|
10
45.5%
|
8
34.8%
|
9
37.5%
|
30
33%
|
| Male |
19
86.4%
|
12
54.5%
|
15
65.2%
|
15
62.5%
|
61
67%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
4.5%
|
0
0%
|
1
4.3%
|
1
4.2%
|
3
3.3%
|
| Not Hispanic or Latino |
16
72.7%
|
19
86.4%
|
17
73.9%
|
23
95.8%
|
75
82.4%
|
| Unknown or Not Reported |
5
22.7%
|
3
13.6%
|
5
21.7%
|
0
0%
|
13
14.3%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
4.3%
|
0
0%
|
1
1.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
4.5%
|
1
4.5%
|
0
0%
|
0
0%
|
2
2.2%
|
| White |
20
90.9%
|
21
95.5%
|
21
91.3%
|
24
100%
|
86
94.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
4.5%
|
0
0%
|
1
4.3%
|
0
0%
|
2
2.2%
|
Outcome Measures
| Title | Percent Change From Baseline in Activated and Memory T Cells |
|---|---|
| Description | The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody in activated and memory T cells with metastatic clear-cell Renal Cell Carcinoma (RCC) |
| Time Frame | Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in the biomarker data set with baseline measurement and at least one on treatment measurement were included in pharmacodynamic analyses. |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Cycle 1 Day 1 |
NA
|
NA
|
NA
|
NA
|
| Cycle 1 Day 2 |
NA
|
NA
|
NA
|
NA
|
| Cycle 1 Day 8 |
NA
|
NA
|
NA
|
NA
|
| Cycle 2 Day 8 |
NA
|
NA
|
NA
|
NA
|
| Cycle 4 Day 1 |
NA
|
NA
|
NA
|
NA
|
| Title | Mean Serum Cytokines: CXCL9 |
|---|---|
| Description | Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10) |
| Time Frame | Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker. |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Cycle 1 Day 1, 3 HRSPOST |
2859.1
(2481.44)
|
2294.3
(1528.97)
|
1906.6
(1744.09)
|
2203.6
(1728.76)
|
| Cycle 1 Day 1, 7HRSPOST |
3287.7
(3617.32)
|
2567.1
(1885.13)
|
2546.1
(2421.00)
|
2883.6
(2827.77)
|
| Cycle 1 Day 2, 24 HRSPOST |
5447.3
(7006.73)
|
4332.3
(3875.12)
|
4216.4
(4715.61)
|
3858.80
(2841.7)
|
| Cycle 2 Day 1, 0 HRSPRE |
5192.6
(4447.78)
|
7220.6
(9385.90)
|
5398.8
(5428.64)
|
5687.4
(6788.78)
|
| Cycle 2 Day 8, 168 HRSPOST |
5271.5
(5196.91)
|
4932.6
(4321.91)
|
5751.3
(5900.87)
|
5773.2
(6560.9)
|
| Cycle 4 Day 1, 0 HRSPRE |
8519.4
(11444.72)
|
5131.2
(4330.84)
|
3523.6
(2678.32)
|
5449.5
(4021.84)
|
| BASELINE |
2681.6
(2135.89)
|
2213.5
(1520.44)
|
2065.3
(1805.25)
|
2610.6
(2118.11)
|
| Title | Mean Serum Cytokines CXCL10 (IP10) |
|---|---|
| Description | Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10) |
| Time Frame | Baseline, Cycle 1 Day 1 3 Hrs Post, Cycle 1 Day 1 7 Hr Post, Cycle 1 Day 2 24 Hr Post, Cycle 2 Day 1 0 Hr Pre, Cycle 2 Day 8 168 Hrs Post, Cycle 4 Day 1 O Hr Pre (~39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker. |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Cycle 1 Day 1, 3 HRSPOST |
525.5
(335.10)
|
523.4
(400.88)
|
422.0
(264.54)
|
450.7
(247.78)
|
| Cycle 1 Day 1, 7HRSPOST |
591.4
(360.30)
|
727.7
(626.98)
|
762.2
(896.22)
|
531.4
(508.20)
|
| Cycle 1 Day 2, 24 HRSPOST |
813.2
(547.71)
|
758.8
(616.06)
|
736.1
(787.53)
|
700.5
(738.71)
|
| Cycle 2 Day 1, 0 HRSPRE |
718.0
(471.22)
|
835.9
(579.07)
|
781.9
(753.41)
|
679.4
(556.47)
|
| Cycle 2 Day 8, 168 HRSPOST |
724.1
(470.03)
|
677.6
(341.15)
|
794.6
(882.64)
|
770.6
(672.43)
|
| Cycle 4 Day 1, 0 HRSPRE |
1272.8
(2075.49)
|
678.7
(364.85)
|
431.3
(133.78)
|
794.8
(574.14)
|
| BASELINE |
474.5
(236.75)
|
483.0
(383.77)
|
397.4
(223.89)
|
767.9
(525.06)
|
| Title | Mean CD4 T Cell Infiltration |
|---|---|
| Description | The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD4 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC). |
| Time Frame | Cycle 2 Day 8 168 Hr post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker evaluable population: All treated participants with at least one measurement for a specific marker were included in the data set for that marker. |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 18 | 20 | 14 | 16 |
| Baseline |
34.1
(78.40)
|
10.4
(34.38)
|
35.2
(77.44)
|
53.2
(109.31)
|
| Cycle 2 Day 8, 168 HrsPost |
64.8
(77.22)
|
28.2
(46.93)
|
53.4
(97.98)
|
107.4
(254.75)
|
| Title | Mean CD8 T Cell Infiltration |
|---|---|
| Description | The objective of the study was to investigate the pharmacodynamic immunomodulatory activity of anti-PD-1 antibody on circulating CD8 infiltrations in tumors in participants with metastatic clear-cell Renal Cell Carcinoma (RCC). |
| Time Frame | 168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker evaluable population: All treated participants at least one measurement for a specific marker were included in the data set for that marker. |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 18 | 20 | 14 | 16 |
| Baseline |
10.2
(13.77)
|
7.8
(10.62)
|
11.9
(14.31)
|
14.4
(18.37)
|
| Cycle 2 Day 8, 169 HRSPOST |
14.9
(13.85)
|
18.9
(17.07)
|
23.3
(23.49)
|
16.3
(22.19)
|
| Title | Best Overall Response in the BMS-936558 Arms |
|---|---|
| Description | Baseline and post-nivolumab treatment modulation of serum levels of interferon-gamma stimulated chemokines CXCL9 and CXCL10 (IP10) were assessed. The participant's best response designation over the study as a whole, recorded between the date of first study drug administration and the date of objectively documented progression per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Time Frame | Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
2
8.3%
|
| Partial Response |
2
9.1%
|
4
18.2%
|
5
21.7%
|
1
4.2%
|
| Stable Disease |
8
36.4%
|
10
45.5%
|
11
47.8%
|
13
54.2%
|
| Progressive Disease |
9
40.9%
|
5
22.7%
|
6
26.1%
|
7
29.2%
|
| Unable To Determine |
2
9.1%
|
3
13.6%
|
0
0%
|
0
0%
|
| Title | Progression Free Survival Rate in BMS-936558 |
|---|---|
| Description | PFS is defined as the time from treatment arm assignment to the date of first documented disease progression. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have any on study tumor assessments will be censored on the date they were assigned a treatment arm. PFS rate is the percentage of participants who did not have disease progression at particular time points (16 weeks, 24 weeks, 48 weeks) |
| Time Frame | Progression free survival rate will be assessed in each individual treatment arm by tumor assessments at 16, 24, and 48 weeks. From initial dose to end of study (assessed up to 39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| 16 weeks |
0.29
|
0.49
|
0.63
|
0.55
|
| 24 weeks |
0
|
0.44
|
0.58
|
0.50
|
| 48 weeks |
0
|
0
|
0.32
|
0.39
|
| Title | Objective Response Rate in BMS-936558 |
|---|---|
| Description | The total number of subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) divided by the total number of participants in the population of interest, and expressed as a percentage. |
| Time Frame | Up to 22 months after study start |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Number (95% Confidence Interval) [percent] |
9.1
|
18.2
|
21.7
|
12.5
|
| Title | Duration of Objective Response for BMS-936558 |
|---|---|
| Description | The duration of response is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. For subjects who neither progress nor die, the duration of response will be censored at the date of their last tumor assessment. |
| Time Frame | The time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death (assessed up to 39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Median (95% Confidence Interval) [weeks] |
30
|
NA
|
48.1
|
NA
|
| Title | Duration of Stable Disease for BMS-936558 as Measured in Participants Whose Best Overall Response is Stable Disease as the Time From Baseline Until the Date of Documented Disease Progression or Death |
|---|---|
| Description | Duration of stable disease (SD) is defined in participants whose BOR is SD at the time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first). Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment |
| Time Frame | The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 22 | 22 | 23 | 24 |
| Median (95% Confidence Interval) [weeks] |
16.5
|
31.4
|
41.3
|
35.1
|
| Title | Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558 |
|---|---|
| Description | Blood samples to evaluate the development of a positive anti-drug antibodies (ADA) response at the doses tested will be collected at time-points pre-dose, C4D1, C8D1 and during follow-up. |
| Time Frame | Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ADA-Positive Subject: A subject with at least one ADA-positive sample at any time after initiation of treatment. ADA-Negative Subject: A subject with no ADA-positive sample after the initiation of treatment |
| Arm/Group Title | Nivolumab 0.3 mg/kg (Previously-treated) | Nivolumab 2 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Previously-treated) | Nivolumab 10 mg/kg (Treatment-naive) |
|---|---|---|---|---|
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. |
| Measure Participants | 17 | 19 | 22 | 21 |
| Anti-Drug Antibody (ADA) positive (%) |
11.8
|
15.8
|
13.6
|
0
|
| Anti-Drug Antibody (ADA) negative(%) |
88.2
|
84.2
|
86.4
|
100
|
Adverse Events
| Time Frame | From first dose to within 100 days of last dose. (10/2011 - 01/2015). From First dose up to 100 days after last dose of study drug, assessed up to January 2017 (approximately 39 months) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | BMS 0.3 mg/kg | BMS 2 mg/kg | BMS 10 mg/kg | BMS 10 mg/Kg-N | ||||
| Arm/Group Description | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to participants who were previously treated with at least one anti-angiogenic therapy. Participants were dosed every 3 weeks until discontinuation or the end of the study. | Nivolumab was administered as a 60 minute IV infusion to treatment-naive participants. Participants were dosed every 3 weeks until discontinuation or the end of the study. | ||||
All Cause Mortality |
||||||||
| BMS 0.3 mg/kg | BMS 2 mg/kg | BMS 10 mg/kg | BMS 10 mg/Kg-N | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| BMS 0.3 mg/kg | BMS 2 mg/kg | BMS 10 mg/kg | BMS 10 mg/Kg-N | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/22 (59.1%) | 11/22 (50%) | 12/23 (52.2%) | 13/24 (54.2%) | ||||
| Cardiac disorders | ||||||||
| Atrial flutter | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Eye disorders | ||||||||
| Papilloedema | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Gastrointestinal disorders | ||||||||
| Colitis | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Constipation | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Enteritis | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Small intestinal haemorrhage | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Gastrointestinal haemorrhage | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Haematemesis | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| General disorders | ||||||||
| Pain | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Pyrexia | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Sudden death | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Bile duct obstruction | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Infections and infestations | ||||||||
| Urinary tract infection | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Viral upper respiratory tract infection | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Sepsis | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Septic shock | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Femur fracture | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Fracture | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Infusion related reaction | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Tendon rupture | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Thermal burn | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Toxicity to various agents | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Aspartate aminotransferase increased | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Blood bilirubin increased | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Amylase increased | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Blood alkaline phosphatase increased | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Blood creatinine increased | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercalcaemia | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Dehydration | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Hyponatraemia | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/22 (0%) | 1/22 (4.5%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Bone pain | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Flank pain | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Polyarthritis | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Basal cell carcinoma | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Malignant melanoma in situ | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Malignant neoplasm progression | 2/22 (9.1%) | 4/22 (18.2%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Metastases to bone | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Metastases to testicle | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Nervous system disorders | ||||||||
| Central nervous system necrosis | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Cerebral haemorrhage | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Tremor | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Ataxia | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Facial nerve disorder | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Ischaemic stroke | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Paralysis | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Peripheral sensory neuropathy | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/22 (4.5%) | 1/22 (4.5%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Renal colic | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Renal failure | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Renal mass | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/22 (0%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Haemothorax | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Hypoxia | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Pleural effusion | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Pleuritic pain | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 0/24 (0%) | ||||
| Pneumonitis | 1/22 (4.5%) | 0/22 (0%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Pneumothorax | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Pulmonary embolism | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Respiratory failure | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Pulmonary fibrosis | 1/22 (4.5%) | 0/22 (0%) | 0/23 (0%) | 0/24 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Embolism | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Thrombosis | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| BMS 0.3 mg/kg | BMS 2 mg/kg | BMS 10 mg/kg | BMS 10 mg/Kg-N | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/22 (100%) | 22/22 (100%) | 23/23 (100%) | 24/24 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 6/22 (27.3%) | 1/22 (4.5%) | 6/23 (26.1%) | 4/24 (16.7%) | ||||
| Endocrine disorders | ||||||||
| Hypothyroidism | 1/22 (4.5%) | 1/22 (4.5%) | 4/23 (17.4%) | 2/24 (8.3%) | ||||
| Eye disorders | ||||||||
| Eye pruritus | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Vision blurred | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/22 (0%) | 1/22 (4.5%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Abdominal distension | 1/22 (4.5%) | 2/22 (9.1%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Abdominal pain | 6/22 (27.3%) | 3/22 (13.6%) | 3/23 (13%) | 5/24 (20.8%) | ||||
| Abdominal pain upper | 3/22 (13.6%) | 1/22 (4.5%) | 2/23 (8.7%) | 1/24 (4.2%) | ||||
| Constipation | 7/22 (31.8%) | 6/22 (27.3%) | 5/23 (21.7%) | 6/24 (25%) | ||||
| Diarrhoea | 4/22 (18.2%) | 4/22 (18.2%) | 5/23 (21.7%) | 9/24 (37.5%) | ||||
| Dry mouth | 1/22 (4.5%) | 2/22 (9.1%) | 1/23 (4.3%) | 5/24 (20.8%) | ||||
| Dyspepsia | 0/22 (0%) | 0/22 (0%) | 3/23 (13%) | 0/24 (0%) | ||||
| Nausea | 8/22 (36.4%) | 7/22 (31.8%) | 6/23 (26.1%) | 10/24 (41.7%) | ||||
| Vomiting | 3/22 (13.6%) | 4/22 (18.2%) | 3/23 (13%) | 3/24 (12.5%) | ||||
| General disorders | ||||||||
| Asthenia | 2/22 (9.1%) | 2/22 (9.1%) | 4/23 (17.4%) | 2/24 (8.3%) | ||||
| Chest pain | 2/22 (9.1%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Chills | 2/22 (9.1%) | 3/22 (13.6%) | 3/23 (13%) | 4/24 (16.7%) | ||||
| Fatigue | 12/22 (54.5%) | 13/22 (59.1%) | 15/23 (65.2%) | 13/24 (54.2%) | ||||
| Mucosal inflammation | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Oedema peripheral | 4/22 (18.2%) | 2/22 (9.1%) | 7/23 (30.4%) | 3/24 (12.5%) | ||||
| Pain | 0/22 (0%) | 4/22 (18.2%) | 4/23 (17.4%) | 0/24 (0%) | ||||
| Pyrexia | 3/22 (13.6%) | 3/22 (13.6%) | 3/23 (13%) | 1/24 (4.2%) | ||||
| Infections and infestations | ||||||||
| Cellulitis | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Rash pustular | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Rhinitis | 3/22 (13.6%) | 0/22 (0%) | 0/23 (0%) | 1/24 (4.2%) | ||||
| Sinusitis | 1/22 (4.5%) | 0/22 (0%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Upper respiratory tract infection | 1/22 (4.5%) | 3/22 (13.6%) | 3/23 (13%) | 4/24 (16.7%) | ||||
| Urinary tract infection | 3/22 (13.6%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Viral upper respiratory tract infection | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 2/24 (8.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 1/22 (4.5%) | 0/22 (0%) | 1/23 (4.3%) | 2/24 (8.3%) | ||||
| Infusion related reaction | 1/22 (4.5%) | 1/22 (4.5%) | 4/23 (17.4%) | 4/24 (16.7%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/22 (9.1%) | 0/22 (0%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Aspartate aminotransferase increased | 1/22 (4.5%) | 0/22 (0%) | 3/23 (13%) | 2/24 (8.3%) | ||||
| Blood alkaline phosphatase increased | 1/22 (4.5%) | 3/22 (13.6%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Blood bilirubin increased | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Blood creatinine increased | 2/22 (9.1%) | 4/22 (18.2%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Weight decreased | 6/22 (27.3%) | 3/22 (13.6%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 7/22 (31.8%) | 3/22 (13.6%) | 3/23 (13%) | 5/24 (20.8%) | ||||
| Dehydration | 0/22 (0%) | 2/22 (9.1%) | 1/23 (4.3%) | 4/24 (16.7%) | ||||
| Hypercalcaemia | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 3/24 (12.5%) | ||||
| Hyperkalaemia | 1/22 (4.5%) | 2/22 (9.1%) | 3/23 (13%) | 2/24 (8.3%) | ||||
| Hypokalaemia | 2/22 (9.1%) | 0/22 (0%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Hyponatraemia | 1/22 (4.5%) | 2/22 (9.1%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Hypophosphataemia | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 3/22 (13.6%) | 2/22 (9.1%) | 6/23 (26.1%) | 9/24 (37.5%) | ||||
| Back pain | 4/22 (18.2%) | 3/22 (13.6%) | 5/23 (21.7%) | 8/24 (33.3%) | ||||
| Flank pain | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Groin pain | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 2/24 (8.3%) | ||||
| Muscular weakness | 2/22 (9.1%) | 1/22 (4.5%) | 1/23 (4.3%) | 2/24 (8.3%) | ||||
| Musculoskeletal chest pain | 2/22 (9.1%) | 2/22 (9.1%) | 2/23 (8.7%) | 4/24 (16.7%) | ||||
| Musculoskeletal pain | 1/22 (4.5%) | 0/22 (0%) | 3/23 (13%) | 2/24 (8.3%) | ||||
| Myalgia | 1/22 (4.5%) | 1/22 (4.5%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Neck pain | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Pain in extremity | 1/22 (4.5%) | 3/22 (13.6%) | 2/23 (8.7%) | 3/24 (12.5%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Malignant neoplasm progression | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 3/22 (13.6%) | 2/22 (9.1%) | 3/23 (13%) | 4/24 (16.7%) | ||||
| Dysgeusia | 1/22 (4.5%) | 0/22 (0%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Headache | 4/22 (18.2%) | 5/22 (22.7%) | 3/23 (13%) | 1/24 (4.2%) | ||||
| Hypoaesthesia | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Restless legs syndrome | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 0/24 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 1/22 (4.5%) | 1/22 (4.5%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Insomnia | 4/22 (18.2%) | 3/22 (13.6%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Mental status changes | 0/22 (0%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 1/22 (4.5%) | 1/22 (4.5%) | 1/23 (4.3%) | 2/24 (8.3%) | ||||
| Urinary retention | 2/22 (9.1%) | 1/22 (4.5%) | 0/23 (0%) | 0/24 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 7/22 (31.8%) | 8/22 (36.4%) | 4/23 (17.4%) | 5/24 (20.8%) | ||||
| Dysphonia | 1/22 (4.5%) | 1/22 (4.5%) | 2/23 (8.7%) | 4/24 (16.7%) | ||||
| Dyspnoea | 1/22 (4.5%) | 5/22 (22.7%) | 2/23 (8.7%) | 5/24 (20.8%) | ||||
| Dyspnoea exertional | 1/22 (4.5%) | 0/22 (0%) | 3/23 (13%) | 1/24 (4.2%) | ||||
| Nasal congestion | 1/22 (4.5%) | 1/22 (4.5%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Oropharyngeal pain | 1/22 (4.5%) | 1/22 (4.5%) | 3/23 (13%) | 1/24 (4.2%) | ||||
| Pneumonitis | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Productive cough | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Pulmonary embolism | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 0/24 (0%) | ||||
| Rhinorrhoea | 2/22 (9.1%) | 1/22 (4.5%) | 1/23 (4.3%) | 1/24 (4.2%) | ||||
| Upper-airway cough syndrome | 0/22 (0%) | 0/22 (0%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dry skin | 1/22 (4.5%) | 1/22 (4.5%) | 1/23 (4.3%) | 3/24 (12.5%) | ||||
| Hyperhidrosis | 1/22 (4.5%) | 2/22 (9.1%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/22 (0%) | 0/22 (0%) | 0/23 (0%) | 2/24 (8.3%) | ||||
| Pruritus | 3/22 (13.6%) | 4/22 (18.2%) | 4/23 (17.4%) | 4/24 (16.7%) | ||||
| Rash | 5/22 (22.7%) | 2/22 (9.1%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
| Rash pruritic | 1/22 (4.5%) | 0/22 (0%) | 2/23 (8.7%) | 1/24 (4.2%) | ||||
| Urticaria | 0/22 (0%) | 0/22 (0%) | 2/23 (8.7%) | 1/24 (4.2%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 1/22 (4.5%) | 2/22 (9.1%) | 2/23 (8.7%) | 2/24 (8.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01358721
Other Study ID Numbers:
- CA209-009
- 2011-005379-18
First Posted:
May 24, 2011
Last Update Posted:
Oct 28, 2021
Last Verified:
Oct 1, 2021