A Phase 1b, Open-label, Multicenter, Multidose, Dose-escalation Study of BMS-936558 (MDX-1106) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 8
- 主要终点
- Number of Participants With a Serious Adverse Event (AE)
研究概览
简要总结
The purpose of this study is to determine the safety and tolerability of treatment with BMS-936558 (MDX-1106) in combination with Ipilimumab (BMS-734016) when given at the same time or as a sequenced regimen in subjects with unresectable Stage III or Stage IV malignant melanoma (MEL)
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
- •For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
- •Inclusion Criteria:
- •Histologic diagnosis of malignant melanoma (MEL)
- •Measurable unresectable Stage III or IV MEL
- •ECOG performance status score of 0 or 1
- •Life expectancy ≥4 months
- •For those enrolled in amendment 5 and later, tumor tissue (archival or recent acquisition) must be available
- •For Cohorts 1-5, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma not including any post-incisional adjuvant therapy. Subjects may be treatment naïve. All metastatic melanoma regardless of primary site of disease will be allowed
- •For Cohorts 6-7, subjects may have been treated with up to 3 prior systemic standard treatments for metastatic melanoma; this does not include any post-incisional adjuvant therapy. Specifically, subjects must have received ≥3 doses of Ipilimumab therapy and the last dose having been administered within 4-12 weeks of initiation of study treatment
排除标准
- •History of severe hypersensitivity reactions to other mAbs
- •Prior malignancy active within the previous 2 years except for localized cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence
- •Active autoimmune disease or a history of known or suspected autoimmune disease
- •History of recently active diverticulitis or symptomatic peptic ulcer disease and history of adrenal insufficiency
- •Regular narcotic analgesia
- •Active, untreated central nervous system metastasis
- •For subjects enrolled in Cohorts 1-5, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody
- •For subjects enrolled in Cohorts 6-7, prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD137 antibodies
- •Any non-oncology vaccine therapy used for prevention of infectious disease
- •Concomitant therapy with any other anti-cancer therapy, concurrent medical conditions requiring use of immunosuppressive medications or use of other investigational drugs
- •Positive tests for human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), hepatitis B, hepatitis C
- •Subjects weighing ≥125 kg are excluded from Cohort 5
- •Subjects in Cohorts 6 and 7 must have received Ipilimumab monotherapy immediately prior to study entry, but must not have received that Ipilimumab as part of a clinical trial
- •Subjects with ocular melanoma are excluded from Cohort 8
研究组 & 干预措施
Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg)
BMS-936558 (MDX1106-04) 0.3 mg/kg solution, 60 minutes intravenous infusion every 3 (q3) weeks for 21 weeks in induction and every 12 (q12) weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: Ipilimumab (Drug)
Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg)
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: Ipilimumab (Drug)
Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg)
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: Ipilimumab (Drug)
Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg)
BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: Ipilimumab (Drug)
Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg)
BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 10 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: Ipilimumab (Drug)
Cohort 8: Nivolumab+Ipilimumab
Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg solution intravenously q3 weeks, 4 doses for 12 weeks
Followed by Nivolumab 3 mg/kg solution alone intravenously q2 weeks, 48 doses for a maximum of 96 weeks
干预措施: Ipilimumab (Drug)
Cohort 1: BMS-936558 (0.3 mg/kg)+Ipilimumab (3 mg/kg)
BMS-936558 (MDX1106-04) 0.3 mg/kg solution, 60 minutes intravenous infusion every 3 (q3) weeks for 21 weeks in induction and every 12 (q12) weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 2: BMS-936558 (1 mg/kg)+Ipilimumab (3 mg/kg)
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 3: BMS-936558 (3 mg/kg)+Ipilimumab (3 mg/kg)
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 4: BMS-936558 (10 mg/kg)+Ipilimumab (3 mg/kg)
BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 3 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 5: BMS-936558 (10 mg/kg)+Ipilimumab (10 mg/kg)
BMS-936558 (MDX1106-04) 10 mg/kg solution, 60 minutes intravenous infusion, q3 weeks for 21 weeks in induction and q12 weeks for 84 weeks in maintenance
Ipilimumab (BMS-734016) 10 mg/kg solution, 90 minutes intravenous infusion, q3 weeks for 9 weeks in induction and q12 weeks for 84 weeks in maintenance
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 6: BMS-936558 (1 mg/kg)
BMS-936558 (MDX1106-04) 1 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 7: BMS-936558 (3 mg/kg)
BMS-936558 (MDX1106-04) 3 mg/kg solution, 60 minutes intravenous infusion, once q2 weeks for a total maximal duration of 96 weeks
干预措施: BMS-936558 (MDX1106-04) (Drug)
Cohort 8: Nivolumab+Ipilimumab
Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg solution intravenously q3 weeks, 4 doses for 12 weeks
Followed by Nivolumab 3 mg/kg solution alone intravenously q2 weeks, 48 doses for a maximum of 96 weeks
干预措施: BMS-936558 (MDX1106-04) (Drug)
结局指标
主要结局
Number of Participants With a Serious Adverse Event (AE)
时间窗: Up to 3 years
incidence of all cause and treatment related serious adverse events
Number of Participants With Select AEs
时间窗: Up to 3 years
incidence of all cause and treatment related Adverse events in certain organ systems
Number of Participants With an Adverse Event (AE)
时间窗: Up to 3 years
incidence of all cause and treatment related adverse events
Number of Participants With an Adverse Event (AE) Which Lead to Discontinuation
时间窗: Up to 3 years
incidence of all cause and treatment related adverse events which lead to discontinuation
Number of Deaths
时间窗: Up to 3 years
incidence of all cause and treatment related deaths
Laboratory Abnormalities: Specific Liver Tests
时间窗: Up to 3 years
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Liver Tests Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
Laboratory Abnormalities: Specific Thyroid Tests
时间窗: Up to 3 years
Number of Participants with On-Treatment Laboratory Abnormalities in Specific Thyroid Tests Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
次要结局
- Objective Response Rate(Up to 3 years)
- Time to Response(Up to 3 Years)
- Duration of Response(from the first documented response (irCR or irPR) until progression or death)
- Progression Free Survival(156 weeks)
- Number of Participants With an Anti-Drug Antibody (ADA) Response for Nivolumab (Nivo) and Ipilimumab (Ipi)(Up to 3 years)
- Peak and Trough Concentrations(Up to 64 Weeks)