Clinical trial NCT01358721: Phase I Biomarker Study (BMS-936558)
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharma USA Inc
First posted: 2011-05-24
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility 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.

Primary outcomes:
measure: Percent Change From Baseline in Activated and Memory T Cells
timeFrame: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1
measure: Mean Serum Cytokines: CXCL9
timeFrame: 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)
measure: Mean Serum Cytokines CXCL10 (IP10)
timeFrame: 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)
measure: Mean CD4 T Cell Infiltration
timeFrame: Cycle 2 Day 8 168 Hr post dose
measure: Mean CD8 T Cell Infiltration
timeFrame: 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 outcomes:
measure: Best Overall Response in the BMS-936558 Arms
timeFrame: Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months)
measure: Progression Free Survival Rate in BMS-936558
timeFrame: 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)
measure: Objective Response Rate in BMS-936558
timeFrame: Up to 22 months after study start
measure: Duration of Objective Response for BMS-936558
timeFrame: 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)
measure: 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
timeFrame: The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months)
measure: Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558
timeFrame: Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Ucsf Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University Of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: The Bunting-Blaustein Cancer Research Building
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Inst
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Upmc Cancer Pavilion
state: Pennsylvania
city: Madison
country: United States
facility: University Of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Villejuif Cedex
country: France
facility: Local Institution
city: Pamplona
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Ross-Macdonald P, Walsh AM, Chasalow SD, Ammar R, Papillon-Cavanagh S, Szabo PM, Choueiri TK, Sznol M, Wind-Rotolo M. Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. J Immunother Cancer. 2021 Mar;9(3):e001506. doi: 10.1136/jitc-2020-001506.
citation: Zhou Q, Qi Y, Wang Z, Zeng H, Zhang H, Liu Z, Huang Q, Xiong Y, Wang J, Chang Y, Bai Q, Xia Y, Wang Y, Liu L, Xu L, Dai B, Guo J, Zhu Y, Zhang W, Xu J. CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma. J Immunother Cancer. 2020 Apr;8(1):e000228. doi: 10.1136/jitc-2019-000228.