AzTrials
AzTrials

Renal Cell CarcinomaPhase 1NCT01358721

Phase I Biomarker Study (BMS-936558)

A Phase 1 study testing BMS-936558 (Anti-PD-1) in people with Renal Cell Carcinoma, run by Bristol-Myers Squibb at 14 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
BMS-936558 (Anti-PD-1)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
14 sitesin 3 countries
Study dates
23 Sep 2011to 22 May 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

United States12 sites

  • The Bunting-Blaustein Cancer Research Building

    Baltimore, Maryland, 21231

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Inst

    Boston, Massachusetts, 02215

  • University Of Chicago Medical Center

    Chicago, Illinois, 60637

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University Of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53705

  • Yale University School Of Medicine

    New Haven, Connecticut, 06520

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Upmc Cancer Pavilion

    Pittsburgh, Pennsylvania, 15232

  • Providence Portland Med Ctr

    Portland, Oregon, 97213

  • Ucsf Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

France1 site

  • Local Institution

    Villejuif, 94805

Other trials in France

Spain1 site

  • Local Institution

    Pamplona, 31192

Other trials in Spain

About this study

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).

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

Read the detailed description

Intervention Model: Parallel Dose Comparison

Being tested
BMS-936558 (Anti-PD-1)
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BMS-936558 (Anti-PD-1)Drug

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

  • BMS-936558 (Anti-PD-1)Drug

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

  • BMS-936558 (Anti-PD-1)Drug

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

Study groups in NCT01358721
Study groupRoleWhat they receive
Arm 1: BMS-936558ExperimentalNot described
Receives: Drug: BMS-936558 (Anti-PD-1)
Arm 2: BMS-936558ExperimentalNot described
Receives: Drug: BMS-936558 (Anti-PD-1)
Arm 3: BMS-936558ExperimentalNot described
Receives: Drug: BMS-936558 (Anti-PD-1)
Arm 4: BMS-936558Experimental(treatment naive)
Receives: Drug: BMS-936558 (Anti-PD-1)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 8, Cycle 4 Day 1

  2. Mean Serum Cytokines: CXCL9

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

    Measured: 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)

  3. Mean Serum Cytokines CXCL10 (IP10)

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

    Measured: 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)

  4. 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).

    Measured: Cycle 2 Day 8 168 Hr post dose

  5. 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).

    Measured: 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 (6)

  1. 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

    Measured: Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (up to approximately 39 months)

  2. 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)

    Measured: 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)

  3. 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.

    Measured: Up to 22 months after study start

  4. 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.

    Measured: 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)

  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

    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

    Measured: The time from treatment arm assignment until the criteria for progression are met or death (whichever occurs first)(assessed up to 39 months)

  6. 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.

    Measured: Pre-dose, Cycle 4 Day 1, Cycle 8 Day 1 and during follow-up.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2011 (estimated)
  2. Study start23 Sep 2011
  3. Primary completion1 Dec 2014
  4. Study completion22 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01358721
Sponsor's protocol ID
CA209-009
Other IDs
2011-005379-18
Status last verified
Oct 2021
First submitted
20 May 2011
Last updated
28 Oct 2021
Data monitoring committee
No

Publications

  • 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.

    PubMed 33658305

  • 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.

    PubMed 32371459

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BMS-936558 (Anti-PD-1) in people with Renal Cell Carcinoma, run by Bristol-Myers Squibb at 14 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01358721, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in