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Phase I Biomarker Study (BMS-936558)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01358721
Recruitment Status : Completed
First Posted : May 24, 2011
Results First Posted : July 26, 2019
Last Update Posted : July 31, 2019
Sponsor:
Collaborator:
Ono Pharma USA Inc
Information provided by (Responsible Party):
Bristol-Myers Squibb

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
Renal Cell Carcinoma Drug: BMS-936558 (Anti-PD-1) Phase 1

Detailed Description:
Intervention Model: Parallel Dose Comparison

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Study Type : Interventional  (Clinical Trial)
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 : August 11, 2011
Actual Primary Completion Date : December 1, 2014
Actual Study Completion Date : May 22, 2019


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




Primary Outcome Measures :
  1. Percent Change From Baseline in Activated and Memory T Cells [ Time Frame: 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)

  2. Mean Serum Cytokines: CXCL9 [ 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) ]
    Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

  3. Mean Serum Cytokines CXCL10 (IP10) [ 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) ]
    Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

  4. Mean CD4 T Cell Infiltration [ Time Frame: 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).

  5. Mean CD8 T Cell Infiltration [ 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) ]
    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 :
  1. Best Overall Response in the BMS-936558 Arms [ Time Frame: 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

  2. Progression Free Survival Rate in BMS-936558 [ 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) ]
    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)

  3. Objective Response Rate in BMS-936558 [ Time Frame: 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.

  4. Duration of Objective Response for BMS-936558 [ 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) ]
    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.

  5. 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 [ 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) ]
    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

  6. Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01358721


Locations
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United States, California
Ucsf Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University Of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Maryland
The Bunting-Blaustein Cancer Research Building
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Inst
Boston, Massachusetts, United States, 02215
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oregon
Providence Portland Med Ctr
Portland, Oregon, United States, 97213
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Upmc Cancer Pavilion
Pittsburgh, Pennsylvania, United States, 15232
United States, Wisconsin
University Of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States, 53705
France
Local Institution
Villejuif Cedex, France, 94805
Spain
Local Institution
Pamplona, Spain, 31192
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharma USA Inc
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01358721    
Other Study ID Numbers: CA209-009
2011-005379-18 ( EudraCT Number )
First Posted: May 24, 2011    Key Record Dates
Results First Posted: July 26, 2019
Last Update Posted: July 31, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents