Phase I Biomarker Study (BMS-936558)
- Conditions
- Renal Cell Carcinoma
- Interventions
- Drug: BMS-936558 (Anti-PD-1)
- Registration Number
- NCT01358721
- Lead Sponsor
- 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.
- Detailed Description
Intervention Model: Parallel Dose Comparison
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 119
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2: BMS-936558 BMS-936558 (Anti-PD-1) - Arm 4: BMS-936558 BMS-936558 (Anti-PD-1) (treatment naive) Arm 3: BMS-936558 BMS-936558 (Anti-PD-1) - Arm 1: BMS-936558 BMS-936558 (Anti-PD-1) -
- Primary Outcome Measures
Name Time Method 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)
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 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
Name Time Method 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
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.
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
Trial Locations
- Locations (13)
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Inst
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Providence Portland Med Ctr
🇺🇸Portland, Oregon, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Upmc Cancer Pavilion
🇺🇸Pittsburgh, Pennsylvania, United States
University Of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Ucsf Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
University Of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The Bunting-Blaustein Cancer Research Building
🇺🇸Baltimore, Maryland, United States
Local Institution
🇪🇸Pamplona, Spain