A Phase 1/2 Study of the Combination of Lirilumab (Anti-KIR) Plus Nivolumab (Anti-PD-1) or Lirilumab Plus Nivolumab and Ipilimumab in Advanced Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 337
- 试验地点
- 24
- 主要终点
- Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5
研究概览
简要总结
To assess the safety and tolerability and preliminary anti-tumor activity of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination. In addition, to assess the combinations of lirilumab and nivolumab or lirilumab and nivolumab plus ipilimumab (BMS-734016) in subjects with advanced (metastatic and/or unresectable) refractory solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
- •During cohort expansion, subjects with various solid tumors that have received at least one and no more than 5 prior treatment regimens
- •Subjects must have measurable disease
- •Subject must consent to provide previously collected tumor tissue
- •Women and men ≥18 years of age with performance status of 0 or 1
- •At least 4 weeks since any previous treatment for cancer
排除标准
- •Active or chronic autoimmune diseases
- •Uncontrolled or significant cardiovascular disease
- •Chronic hepatitis (except for subjects with hepatocellular carcinoma)
- •Active infection
- •Active Central nervous system (CNS) metastases
- •Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome((HIV/AIDS)
- •Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Part 1
Dose Escalation and Initial Signal Detection in Multiple Solid Tumors - Nivolumab with Lirilumab
干预措施: Lirilumab (Drug)
Part 1
Dose Escalation and Initial Signal Detection in Multiple Solid Tumors - Nivolumab with Lirilumab
干预措施: Nivolumab (Drug)
Part 2 and 3: Cohort Expansion
In platinum-refractory recurrent or metastatic SCCHN - Nivolumab with or without Lirilumab
干预措施: Lirilumab (Drug)
Part 2 and 3: Cohort Expansion
In platinum-refractory recurrent or metastatic SCCHN - Nivolumab with or without Lirilumab
干预措施: Nivolumab (Drug)
Part 4: Cohort Expansion
Additional Signal Detection in Solid Tumors - Nivolumab with Lirilumab (Study Part 4 Removed; No Subjects Enrolled)
干预措施: Lirilumab (Drug)
Part 4: Cohort Expansion
Additional Signal Detection in Solid Tumors - Nivolumab with Lirilumab (Study Part 4 Removed; No Subjects Enrolled)
干预措施: Nivolumab (Drug)
Part 5 and 6
Safety Lead-In and Additional Signal Detection in Solid Tumors -- Nivolumab Plus Ipilimumab with Lirilumab (Study Part 6 Removed; No Subjects Enrolled)
干预措施: Lirilumab (Drug)
Part 5 and 6
Safety Lead-In and Additional Signal Detection in Solid Tumors -- Nivolumab Plus Ipilimumab with Lirilumab (Study Part 6 Removed; No Subjects Enrolled)
干预措施: Nivolumab (Drug)
Part 5 and 6
Safety Lead-In and Additional Signal Detection in Solid Tumors -- Nivolumab Plus Ipilimumab with Lirilumab (Study Part 6 Removed; No Subjects Enrolled)
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5
时间窗: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5
时间窗: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5
时间窗: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.
The Number of Participant Deaths in the Study - Parts 1, 2 and 5
时间窗: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
The number of participants who died.
Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5
时间窗: From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)
Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time.
Objective Response Rate (ORR)
时间窗: From first dose up to approximately 2.5 years
Objective Response Rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR for a participant was derived using investigator-provided tumor measurements per RECIST v1.1. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Progression Free Survival Rate (PFSR) at 6 Months - Part 3(At 6 months after first dose)
- Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri)(Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.)
- Disease Control Rate (DCR) - Part 3(From first dose up to approximately 2.5 years)
- Median Duration of Response (mDOR) - Parts 3 and 5(From first dose to the date of the first documented tumor progression as determined or death due to any cause, whichever occurs first. (Up to approximately 2.5 years))
- Median Time to Response (mTTR) - Part 3(From date of first dose of study medication to the date of the first documented objective response (up to approximately 2.5 years))
- The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5(From first dose until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. (Up to approximately 2.5 years))
- Overall Survival (OS) - Part 3(From date of first dose of study medication to the date of death for any cause. (Up to approximately 2.5 years))
- Number of Participants With Adverse Events (AEs) - Part 3(From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years))
- Number of Participants With Serious Adverse Events (SAEs) - Part 3(From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years))
- Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3(From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years))
- The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5(Pre-dose Day 1 (Cycles 1 ,3 ,5, 7, 9), Pre-dose Day 29 (Cycle 1, 2))
- Progression Free Survival (PFS) - Part 3(From first dose to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. (Up to approximately 2.5 years))
- The Number of Participant Deaths in the Study - Part 3(From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years))
- Half-life (T-HALF) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Ctrough - Parts 1, 2 and 5 (Liri)(Pre-dose on cycle 1 day 29 and Pre-dose and end of infusion on cycle 2 day 29.)
- Number of Participants With Clinical Laboratory Test Abnormalities - Part 3(From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years))
- Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5(From first dose to 100 days after last dose (up to approximately 126 weeks))
- Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Clearance Per Time (CLT) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5(Pre-dose, end of infusion, 24, 168, and 336 hours post dose on day 1 cycle 1 and pre-dose on day 29 cycle 1. Pre-dose, end of infusion, 24 and 168 hours post dose on cycle 2 day 29.)
- End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo)(Pre-dose and end of infusion on cycle 1 day 1 and cycle 2 day 29.)
- Ctrough - Parts 1, 2 and 5 (Nivo)(336 hours post dose on cycle 1 day 1 (cycle 1 day 15) and pre-dose and end of infusion on cycle 2 day 29.)