A Phase 1/2a Study of BMS-986205 Administered in Combination With Nivolumab (Anti-PD-1 Monoclonal Antibody) and in Combination With Both Nivolumab and Ipilimumab (Anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 627
- 试验地点
- 47
- 主要终点
- Number of Treated Participant With Laboratory Abnormalities - Liver
研究概览
简要总结
The purpose of the study is to determine safety and effectiveness of experimental medication BMS-986205 when combined with Nivolumab and in combination with both Nivolumab and Ipilimumab in patients with cancers that are advanced or have spread. Pharmacokinetics and pharmacodynamics of BMS-986205 when combined with Nivolumab and in combination with Nivolumab and Ipilimumab in this patient population will also be assessed.
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
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（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 that have progressed following at least one standard regimen
- •During cohort expansion, subjects with advanced cancer that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
- •Subjects must have measurable disease
- •Subject must consent to provide previously collected tumor tissue and a tumor biopsy during screening.
- •At least 4 weeks since any previous treatment for cancer
- •Must be able to swallow pills or capsules
- •Eastern Cooperative Oncology Group(ECOG) Performance Status 0-1
排除标准
- •Active or chronic autoimmune diseases
- •Uncontrolled or significant cardiovascular disease
- •History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS)
- •Chronic hepatitis: Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
- •Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
- •Active infection
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Combination Therapy (Dose Escalation)
BMS 986205 + Nivolumab specified dose at specified intervals.
干预措施: BMS-986205 (Drug)
Combination Therapy (Dose Escalation)
BMS 986205 + Nivolumab specified dose at specified intervals.
干预措施: Nivolumab (Drug)
Combination Therapy (Dose Expansion)
BMS 986205 + Nivolumab specified dose at specified intervals.
干预措施: BMS-986205 (Drug)
Combination Therapy (Dose Expansion)
BMS 986205 + Nivolumab specified dose at specified intervals.
干预措施: Nivolumab (Drug)
Combination Therapy 2 (Dose Expansion)
BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
干预措施: BMS-986205 (Drug)
Combination Therapy 2 (Dose Expansion)
BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
干预措施: Nivolumab (Drug)
Combination Therapy 2 (Dose Expansion)
BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of Treated Participant With Laboratory Abnormalities - Liver
时间窗: From first dose to 100 days after last dose (up to 15 months)
The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Results reported in International System of Units (SI)
Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths
时间窗: From first dose to 100 days after last dose (up to 15 months)
Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation and deaths.
Number of Treated Participant With Laboratory Abnormalities - Thyroid
时间窗: From first dose to 100 days after last dose (up to 15 months)
The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Results reported in International System of Units (SI)
Percentage of Participants With an Objective Response Rate (ORR)- Parts 2 and 3
时间窗: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Objective response rate (ORR) is defined as the percentage of all treated participants whose BOR is either a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Progression Free Survival Rate (PFSR) at 24 Weeks - Parts 2 and 3
时间窗: At 24 weeks after first dose
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 24 weeks. Reported values are estimates derived from Kaplan-Meier analyses.
Progression Free Survival Rate (PFSR) at 1 Year - Parts 2 and 3
时间窗: At 1 year
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 1 year. Reported values are estimates derived from Kaplan-Meier analyses.
Number of Participants With a Best Overall Response (BOR) - Parts 2 and 3
时间窗: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Best overall response (BOR) is defined as the best response designation over the study as a whole. Complete response (CR) or partial response (PR) determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. For those participants who have surgical resection, only pre-surgical tumor assessments will be considered in the determination of BOR. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease. (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Median Duration of Response (DoR) - Parts 2 and 3
时间窗: From first dose to the date of disease progression, death, or until participants withdraw from the study, whichever occurs first (up to a maximum of 185 weeks)
Duration of response (DoR) was computed for all treated subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Progression Free Survival Rate (PFSR) at 2 Years - Parts 2 and 3
时间窗: At 2 years
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 2 years. Reported values are estimates derived from Kaplan-Meier analyses.
次要结局
- CLT/F(At Cycle 0 Day 14 [cycle 0 = up to 2 weeks])
- Percent Change From Baseline in Serum Kynurenine(At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks])
- Cmax(At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks])
- Accumulation Index (AI) - AUC(TAU)(Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose))
- Accumulation Index (AI) - Cmax(At Cycle 0 Day 14 [cycle 0 = up to 2 weeks])
- Tmax(At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks])
- Progression Free Survival Rate (PFSR) at 24 Weeks - Part 1 and Clinical Pharmacology Substudies(At 24 weeks after first dose)
- Ctrough(At cycles 0 [up to 2 weeks] and at cycles 3, 5, 7, 10, 11, 13, 15 [each cycle is up to 4 weeks])
- Percentage of Participants With an Objective Response Rate (ORR) - Part 1 and Clinical Pharmacology Substudies(From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks))
- AUC(TAU)(Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose))
- Change From Baseline in Serum Kynurenine(At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks])
- Number of Participants With a Best Overall Response (BOR) - Part 1 and Clinical Pharmacology Substudies(From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks))
- Progression Free Survival Rate (PFSR) at 1 Year - Part 1 and Clinical Pharmacology Substudies(At 1 year)
- Median Duration of Response (DoR) - Part 1 and Clinical Pharmacology Substudies(From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks))
- Progression Free Survival Rate (PFSR) at 2 Years - Part 1 and Clinical Pharmacology Substudies(At 2 years)
- Number of Participants With a Positive Anti-Drug Antibody (ADA) Test(From first dose to last dose (up to approximately 48 weeks))