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A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00730639
First Posted: August 8, 2008
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
August 4, 2008
August 8, 2008
February 22, 2016
April 15, 2016
November 21, 2017
January 22, 2009
February 4, 2013   (Final data collection date for primary outcome measure)
  • Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs [ Time Frame: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years ]

    AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.

    SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

  • Number of Participants With Abnormal Serum Chemistry Laboratory Values [ Time Frame: Day 1 up to June 2013, approximately 4 years ]
    Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine and Total Bilirubin. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.
  • Number of Participants With Abnormal Hematology Laboratory Values [ Time Frame: Day 1 up to June 2013, approximately 4 years ]
    Hemoglobin, Lymphocytes, Neutrophils, Platelets and Leukocytes. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for Hemoglobin were based on Gr 1: 10.0 - less than (<) lower limit of normal (LLN); Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for Neutrophils were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < lower limits of normal (LLN); Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0. Abnormal values for Leukocytes were based on Gr 1: 3.0 - < LLN; Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0.
To characterize the safety and tolerability of multiple doses of MDX-1106 [ Time Frame: Up to 12 eight (8) week cycles, each cycle is comprised of 4 doses, on days 1,15,29,and 43 ]
Complete list of historical versions of study NCT00730639 on ClinicalTrials.gov Archive Site
  • Immunogenicity Assessment [ Time Frame: Day 1 up to June 2013, approximately 4 years ]
    Classification of participants host immune response was based on the following definitions: Anti-Drug Antibody (ADA) Positive Subjects have with at least one ADA positive sample at any time after initiation of treatment. ADA positive subjects were further classified into categories with Persistent Positive defined as an ADA positive sample at 2 or more sequential timepoints at least 8 weeks apart.
  • Objective Response Rate [ Time Frame: Day 1 up to June 2013, approximately 4 years ]
    Tumor response was evaluated by the sponsor based on tumor assessments by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate (ORR) was defined as the proportion of participants who's confirmed best overall response (BOR) is either complete (CR) or partial (PR), where the denominator is the number of treated participants in the population of interest. Response was based on tumor measurements. Responders= complete response (CR) or partial response (PR). CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. 95% Confidence intervals (CIs) were computed using the Clopper Pearson method.
  • Duration of Tumor Response [ Time Frame: Day 1 up to June 2013, approximately 4 years ]
    Duration of tumor response (DOR) was calculated from the first date of response of complete response (CR) or partial response (PR) to the date of the first progressive disease (PD) or the date of death. Duration of response was censored at the last tumor assessment date if a responder did not have PD or death. Nonresponders were not included in the analysis. Median DOR was estimated by Kaplan-Meier analysis.
  • Geometric Mean Maximum Serum Concentration (Cmax) [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]
    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA). Blood samples were assessed at all doses from a subset of participants. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).
  • Median Time of Maximum Serum Concentration (Tmax) [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]
    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed Blood samples were assessed at all doses from a subset of participants. The PK parameter of Tmax was measured in hours (h).
  • Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3 ]
    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of AUC was measured in micrograms*hours per milliliter (μg*h/mL).
  • Geometric Mean Total Body Clearance of Drug From Serum (CLT) [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3 ]
    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples Blood samples were assessed at all doses from a subset of participants. The PK parameter of CLT was measured in milliliters per hour (mL/h).
  • Mean Effective Half-life (T-HALFeff) [ Time Frame: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3 ]
    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of T-HALFeff was measured in hours (h).
  • Immunogenicity and PK of multiple doses [ Time Frame: up to 12 eight week cycles ]
  • Assess the efficacy of MDX-1106 as monotherapy [ Time Frame: up to 12 eight week cycles ]
Not Provided
Not Provided
 
A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies
A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies
The purpose of this study is to determine the safety and effectiveness of MDX-1106 in patients with certain types of cancer. Another purpose is to determine how MDX-1106 is absorbed and distributed within the body, and how it's eventually eliminated.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Metastatic Castration-resistant Prostrate Cancer
  • Renal Cell Carcinoma
  • Metastatic Melanoma
  • Non-small Cell Lung Cancer
  • Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Name: BMS-936558
  • Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Name: BMS-936558
  • Biological: BMS-936558 (MDX-1106)
    Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
    Other Name: BMS-936558
  • Experimental: Melanoma - BMS-936558 (MDX-1106)
    Intervention: Biological: BMS-936558 (MDX-1106)
  • Experimental: RCC - BMS-936558 (MDX-1106)
    Intervention: Biological: BMS-936558 (MDX-1106)
  • Experimental: mCRPC - BMS-936558 (MDX-1106)
    Intervention: Biological: BMS-936558 (MDX-1106)
  • Experimental: NSCLC - BMS-936558 (MDX-1106)
    Intervention: Biological: BMS-936558 (MDX-1106)
  • Experimental: CRC - BMS-936558 (MDX-1106)
    Intervention: Biological: BMS-936558 (MDX-1106)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
395
May 21, 2018
February 4, 2013   (Final data collection date for primary outcome measure)

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Subjects must have mCRPC,RCC, MEL, Non-small-cell lung cancer (NSCLC), or Colorectal Cancer (CRC), that is advanced (non-resectable), or recurrent and for which no alternative, curative standard exists
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Must have at least 1 measurable lesion
  • Subjects with mCRPC and with only non-measurable bone lesions must have either progression new lesions or have Prostate-specific antigen (PSA) progression within the 6-week period before study administration
  • At least 1 and up to 5 prior systemic therapies for advanced/recurrent disease
  • Prior treated brain or meningeal metastases must be without Magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids for at least 2 weeks before study drug administration
  • Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids must be discontinued at least 2 weeks before study drug administration
  • Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration

Exclusion Criteria:

  • History of severe hypersensitivity reactions to other Monoclonal antibody (mAb)s
  • Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
  • Prior therapy with an anti-Programmed death-1 (PD-1), anti-PD-L1, anti-PD-L2, or anti- Cytotoxic t-lymphocyte antigen-4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)
  • Known history of Human Immunodeficiency Virus
  • Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
  • Underlying medical conditions that will make the administration of study drug hazardous
  • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
  • Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00730639
CA209-003
MDX1106-03 ( Other Identifier: BMS )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP