A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies
- Conditions
- Metastatic MelanomaMetastatic Castration-resistant Prostrate CancerRenal Cell CarcinomaNon-small Cell Lung Cancer
- Interventions
- Biological: BMS-936558 (MDX-1106)
- Registration Number
- NCT00730639
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 395
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NSCLC - BMS-936558 (MDX-1106) BMS-936558 (MDX-1106) - RCC - BMS-936558 (MDX-1106) BMS-936558 (MDX-1106) - Melanoma - BMS-936558 (MDX-1106) BMS-936558 (MDX-1106) - CRC - BMS-936558 (MDX-1106) BMS-936558 (MDX-1106) - mCRPC - BMS-936558 (MDX-1106) BMS-936558 (MDX-1106) -
- Primary Outcome Measures
Name Time Method Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs 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 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 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate 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.
Immunogenicity Assessment 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.
Geometric Mean Maximum Serum Concentration (Cmax) 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) 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 Total Body Clearance of Drug From Serum (CLT) 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) 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).
Duration of Tumor Response 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 Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose 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).
Trial Locations
- Locations (13)
Pinnacle Oncology Hematology
🇺🇸Scottsdale, Arizona, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Vanderbilt-Ingram Cancer Ctr
🇺🇸Nashville, Tennessee, United States
Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Carolina Biooncology Institute
🇺🇸Huntersville, North Carolina, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Nassau
🇺🇸New York, New York, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University Of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States