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:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00730639
First received: August 4, 2008
Last updated: March 24, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Metastatic Castration-resistant Prostrate Cancer (mCRPC)
Renal Cell Carcinoma (RCC)
Metastatic Melanoma (MEL)
Non-small Cell Lung Cancer (NSCLC)
Biological: BMS-936558 (MDX-1106)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Immunogenicity Assessment [ Time Frame: Day 1 up to June 2013, approximately 4 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 395
Study Start Date: January 2009
Estimated Study Completion Date: November 2016
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Melanoma - BMS-936558 (MDX-1106) 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
Experimental: RCC - BMS-936558 (MDX-1106) Biological: BMS-936558 (MDX-1106)
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Other Name: BMS-936558
Experimental: mCRPC - BMS-936558 (MDX-1106) Biological: BMS-936558 (MDX-1106)
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Other Name: BMS-936558
Experimental: NSCLC - BMS-936558 (MDX-1106) Biological: BMS-936558 (MDX-1106)
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Other Name: BMS-936558
Experimental: CRC - BMS-936558 (MDX-1106) Biological: BMS-936558 (MDX-1106)
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Other Name: BMS-936558

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00730639

Locations
United States, Arizona
Pinnacle Oncology Hematology
Scottsdale, Arizona, United States, 85258
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University Of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Carolina Biooncology Institute
Huntersville, North Carolina, United States, 28078
United States, Ohio
Christ Hospital
Cincinnati, Ohio, United States, 45219
United States, Tennessee
Vanderbilt-Ingram Cancer Ctr
Nashville, Tennessee, United States, 37232
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00730639     History of Changes
Other Study ID Numbers: CA209-003  MDX1106-03 
Study First Received: August 4, 2008
Results First Received: February 22, 2016
Last Updated: March 24, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Adenocarcinoma
Bronchial Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Kidney Diseases
Kidney Neoplasms
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on April 27, 2016