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Completed

NCT Number: NCT01358721

Phase I Biomarker Study (BMS-936558)

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

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Key information

Conditions

Renal Cell Carcinoma Adenocarcinoma Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Local Institution, Villejuif, France

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About this study

Intervention Model: Parallel Dose Comparison

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BMS-936558 (Anti-PD-1)

Drug

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

Primary outcomes

  1. 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 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)

  2. Mean Serum Cytokines: CXCL9

    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)

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

  3. Mean Serum Cytokines CXCL10 (IP10)

    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)

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

  4. Mean CD4 T Cell Infiltration

    Time frame: 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).

  5. Mean CD8 T Cell Infiltration

    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)

    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 outcomes

  1. Best Overall Response in the BMS-936558 Arms

    Time frame: 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

  2. Progression Free Survival Rate in BMS-936558

    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)

    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)

  3. Objective Response Rate in BMS-936558

    Time frame: 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.

  4. Duration of Objective Response for BMS-936558

    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)

    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.

  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

    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)

    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

  6. Immunogenicity of BMS-936558 as Measured by the Detection of Human Antibodies Against BMS-936558

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Collaborators

  • Ono Pharma USA Inc

Registry information

Official study 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).

Important dates

Study start
2011
Primary completion
2014
Study completion
2019
First posted
May 24, 2011
Registry last updated
Oct 28, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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