A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 395
- 试验地点
- 25
- 主要终点
- Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Objective Response Rate(Day 1 up to June 2013, approximately 4 years)
- 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)
- Immunogenicity Assessment(Day 1 up to June 2013, approximately 4 years)
- 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)
- 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)
- 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)
- Mean Effective Half-life (T-HALFeff)(1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3)
- Duration of Tumor Response(Day 1 up to June 2013, approximately 4 years)