Phase I Biomarker Study (BMS-936558)

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BMS-936558 (Anti-PD-1)

About this trial

This is an interventional basic science trial for Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm 1: BMS-936558

Arm 2: BMS-936558

Arm 3: BMS-936558

Arm 4: BMS-936558

Arm Description

(treatment naive)

Outcomes

Primary Outcome Measures

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)

Mean Serum Cytokines: CXCL9

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

Mean Serum Cytokines CXCL10 (IP10)

Objective is to investigate the pharmacodynamic immunomodulatory activity of serum chemokines (CXCL9, CXCL10)

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).

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).

Secondary Outcome Measures

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

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)

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.

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.

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

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.

Full Information

NCT ID

NCT01358721

First Posted

May 20, 2011

Last Updated

October 13, 2021

Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharma USA Inc

1. Study Identification

Unique Protocol Identification Number

NCT01358721

Brief Title

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

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

September 23, 2011 (Actual)

Primary Completion Date

December 1, 2014 (Actual)

Study Completion Date

May 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

Collaborators

Ono Pharma USA Inc

4. Oversight

Data Monitoring Committee

No

5. 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.

Detailed Description

Intervention Model: Parallel Dose Comparison

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Cell Carcinoma

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

119 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: BMS-936558

Arm Type

Experimental

Arm Title

Arm 2: BMS-936558

Arm Type

Experimental

Arm Title

Arm 3: BMS-936558

Arm Type

Experimental

Arm Title

Arm 4: BMS-936558

Arm Type

Experimental

Arm Description

(treatment naive)

Intervention Type

Drug

Intervention Name(s)

BMS-936558 (Anti-PD-1)

Intervention Description

Solution, Intravenous infusion, 0.3 mg/kg, Every 3 weeks, Indefinitely depending on response

Intervention Type

Drug

Intervention Name(s)

BMS-936558 (Anti-PD-1)

Intervention Description

Solution, Intravenous infusion, 2 mg/kg, Every 3 weeks, Indefinitely depending on response

Intervention Type

Drug

Intervention Name(s)

BMS-936558 (Anti-PD-1)

Intervention Description

Solution, Intravenous infusion, 10 mg/kg, Every 3 weeks, Indefinitely depending on response

Primary Outcome Measure Information:

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

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)

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)

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

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)

Secondary Outcome Measure Information:

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)

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)

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

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)

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)

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Ucsf Helen Diller Family Comprehensive Cancer Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

Yale University School Of Medicine

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

H. Lee Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

University Of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

The Bunting-Blaustein Cancer Research Building

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Dana Farber Cancer Inst

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Providence Portland Med Ctr

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

Facility Name

Fox Chase Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111

Country

United States

Facility Name

Upmc Cancer Pavilion

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

Facility Name

University Of Wisconsin Carbone Cancer Center

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53705

Country

United States

Facility Name

Local Institution

City

Villejuif Cedex

ZIP/Postal Code

94805

Country

France

Facility Name

Local Institution

City

Pamplona

ZIP/Postal Code

31192

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

33658305

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.

Results Reference

derived

PubMed Identifier

32371459

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.

Results Reference

derived

Links:

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

BMS Clinical Trial Information

URL

https://www.bmsstudyconnect.com/s/US/English/USenHome

Description

BMS Clinical Trial Patient Recruiting

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

Investigator Inquiry Form

URL

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

Description

FDA Safety Alerts and Recalls

Renal Cell Carcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial