Phase I Biomarker Study (BMS-936558)

Renal Cell Carcinoma Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01358721
• Other study ID #: CA209-009
• Secondary ID: 2011-005379-18
• Status: Completed
• Phase: Phase 1
• Start date: September 23, 2011
• Est. completion date: May 22, 2019

Study information

• Verified date: October 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the pharmacodynamic and biologic properties of BMS-936558 in subjects with metastatic renal cell carcinoma.

Description:

Intervention Model: Parallel Dose Comparison

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: May 22, 2019
• Est. primary completion date: December 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 0.3 mg/kg, Every 3 weeks, Indefinitely depending on response
• BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 2 mg/kg, Every 3 weeks, Indefinitely depending on response
• BMS-936558 (Anti-PD-1)
Solution, Intravenous infusion, 10 mg/kg, Every 3 weeks, Indefinitely depending on response

Locations

Country	Name	City	State
France	Local Institution	Villejuif Cedex
Spain	Local Institution	Pamplona
United States	The Bunting-Blaustein Cancer Research Building	Baltimore	Maryland
United States	Dana Farber Cancer Inst	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	University Of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Upmc Cancer Pavilion	Pittsburgh	Pennsylvania
United States	Providence Portland Med Ctr	Portland	Oregon
United States	Ucsf Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharma USA Inc

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Activated and Memory T Cells	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)	Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1
Primary	Mean Serum Cytokines: CXCL9	Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)	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)
Primary	Mean Serum Cytokines CXCL10 (IP10)	Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)	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)
Primary	Mean CD4 T Cell Infiltration	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).	Cycle 2 Day 8 168 Hr post dose
Primary	Mean CD8 T Cell Infiltration	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).	168 hour post does Cycle 2 Day 8 in evaluable participates (First active dose of study medication to cycle two day eight post injection)
Secondary	Best Overall Response in the BMS-936558 Arms	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	Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months)
Secondary	Progression Free Survival Rate in BMS-936558	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)	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)
Secondary	Objective Response Rate in BMS-936558	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.	Up to 22 months after study start
Secondary	Duration of Objective Response for BMS-936558	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.	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)
Secondary	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	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	The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months)
Secondary	Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558	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.	Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry Form