An Open-Label Phase 1b/2 Study of E7389 Liposomal Formulation Plus Nivolumab in Subjects With Solid Tumor
概览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 125
- 试验地点
- 19
- 主要终点
- Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs)
概览
简要总结
The primary purpose of the study is to evaluate safety and tolerability of E7389 liposomal formulation (E7389-LF) in combination with nivolumab and to determine the recommended Phase 2 dose (RP2D) in Phase 1b part and to evaluate objective response rate (ORR) of E7389-LF and nivolumab using RP2D in each tumor type in Phase 2 part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 1b part only: Participants with advanced, nonresectable, or recurrent solid tumor for which no alternative standard therapy or no effective therapy exists (participants who will be the candidate of treatment by nivolumab monotherapy as standard therapy is acceptable)
- •Phase 2 part only: Participants with a confirmed diagnosis of nonresectable gastric cancer (GC), esophageal cancer (EGC) or small cell lung cancer (SCLC) who showed disease progression based on investigator's assessment during or after first line chemotherapy (second-line chemotherapy for GC) and did not receive any other systemic chemotherapy to advanced/recurrent disease
- •Participants who meet the following criteria for biopsy; Phase 1b part: Participants who have accessible tumors for biopsy and agree to tumor biopsy for pre- and post-treatment of study drug (If a pre-treatment biopsy cannot be obtained due to safety issue, then an archival tumor tissue sample may be submitted.) Phase 2 part: Participants who have accessible tumors for biopsy and agree with tumor biopsy for pre and post treatment of study drug (As an alternative to pre-treatment biopsy, tumor tissue sample taken from recurrent or advanced disease may be submitted). However, if the sponsor and the investigator discuss and agree in advance, and the participants agree to submission of archival tumor tissue, then these participants are eligible regardless of accessible tumors, and consent to biopsy is not necessary
- •Life expectancy of greater than or equal to (\>=) 12 weeks
- •Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1
- •Phase 2 part only: At least one measurable lesion based on RECIST 1.1 (Lesions that have had radiotherapy or loco-regional therapies must show evidence of progressive disease to be deemed a measurable lesion)
排除标准
- •Diagnosed with meningeal carcinomatosis
- •Participants with brain or subdural metastases or invasion are not eligible
- •Active, known, or suspected autoimmune disease
研究组 & 干预措施
Phase 1b, Cohort 3: E7389-LF Dose 3 + Nivolumab Dose 2
Participants will receive E7389-LF (intravenous) Dose 3 and nivolumab (intravenous) Dose 2 on specified days.
干预措施: E7389-LF (Drug)
Phase 1b, Cohort 1: E7389-LF Dose 1 + Nivolumab Dose 1
Participants will receive E7389-LF (intravenous) Dose 1 and nivolumab (intravenous) Dose 1 on specified days.
干预措施: E7389-LF (Drug)
Phase 1b, Cohort 1: E7389-LF Dose 1 + Nivolumab Dose 1
Participants will receive E7389-LF (intravenous) Dose 1 and nivolumab (intravenous) Dose 1 on specified days.
干预措施: Nivolumab (Drug)
Phase 1b, Cohort 2: E7389-LF Dose 2 + Nivolumab Dose 1
Participants will receive E7389-LF (intravenous) Dose 2 and nivolumab (intravenous) Dose 1 on specified days.
干预措施: E7389-LF (Drug)
Phase 1b, Cohort 2: E7389-LF Dose 2 + Nivolumab Dose 1
Participants will receive E7389-LF (intravenous) Dose 2 and nivolumab (intravenous) Dose 1 on specified days.
干预措施: Nivolumab (Drug)
Phase 1b, Cohort 3: E7389-LF Dose 3 + Nivolumab Dose 2
Participants will receive E7389-LF (intravenous) Dose 3 and nivolumab (intravenous) Dose 2 on specified days.
干预措施: Nivolumab (Drug)
Phase 1b, Cohort 4: E7389-LF Dose 4 + Nivolumab Dose 2
Participants will receive E7389-LF (intravenous) Dose 4 and nivolumab (intravenous) Dose 2 on specified days.
干预措施: E7389-LF (Drug)
Phase 1b, Cohort 4: E7389-LF Dose 4 + Nivolumab Dose 2
Participants will receive E7389-LF (intravenous) Dose 4 and nivolumab (intravenous) Dose 2 on specified days.
干预措施: Nivolumab (Drug)
Phase 2, Cohort-1: E7389-LF + Nivolumab
Participants with gastric cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: E7389-LF (Drug)
Phase 2, Cohort-1: E7389-LF + Nivolumab
Participants with gastric cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: Nivolumab (Drug)
Phase 2, Cohort-2: E7389-LF + Nivolumab
Participants with esophageal cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: E7389-LF (Drug)
Phase 2, Cohort-2: E7389-LF + Nivolumab
Participants with esophageal cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: Nivolumab (Drug)
Phase 2, Cohort-3: E7389-LF + Nivolumab
Participants with small lung cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: E7389-LF (Drug)
Phase 2, Cohort-3: E7389-LF + Nivolumab
Participants with small lung cancer will receive RP2D of E7389-LF (intravenous) and nivolumab (intravenous) determined in Phase 1b part.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Baseline up to Cycle 1 (Cycle length is equal to [=] up to 28 days)
DLTs are defined as study drug related adverse events (AEs). Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Phase 2: ORR
时间窗: Baseline up to End of Treatment (Up to approximately 79 months)
ORR is defined as the percentage of participants who have best overall response of complete response (CR) or partial response (PR). The ORR will be assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version 1.1.
次要结局
- Phase 1b and Phase 2: Number of Participants With AEs and Serious Adverse Events (SAEs)(Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment, whichever shorter (up to approximately 79 months))
- Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Laboratory Evaluations(Baseline up to End of Treatment (Up to approximately 79 months))
- Phase 1b and Phase 2: Number of Participants With Markedly Abnormal Vital Signs(Baseline up to End of Treatment (Up to approximately 79 months))
- Phase 1b and Phase 2: Number of Participants With Clinically Abnormal 12-lead Electrocardiogram (ECG)(Baseline up to End of Treatment (Up to approximately 79 months))
- Phase 1b and Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)(Baseline up to End of Treatment (Up to approximately 79 months))
- Phase 1b and 2: Number of Participants With Clinically Significant Abnormal Physical Examination Findings(Baseline up to End of Treatment (Up to approximately 79 months))
- Phase 1b and Phase 2, Cmax: Maximum Observed Plasma Concentration of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 1b and Phase 2: Serum Concentration of Nivolumab(Up to Cycle 13 (each Cycle length = up to 28 days))
- Phase 1b and Phase 2, Tmax: Time to Maximum Observed Plasma Concentration (Cmax) of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 1b and Phase 2, AUC: Area Under the Plasma Concentration-time Curve Over Time From 0 to Last Measurable Concentration of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 1b and Phase 2, T1/2: Terminal Phase Elimination Half-life of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 1b and Phase 2, CL: Total Body Clearance of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 1b and Phase 2, Vd: Volume of Distribution of E7389-LF(Phase 1b, Cycle 1 Day 1: 0 to 24 hours, Cycle 1 Days 4 and 8; Phase 2, Cycle 1 Days 1 and 8 (Cycle length = up to 28 days))
- Phase 2: Progression-Free Survival (PFS)(From the first does of the study drug up to the first documentation of disease progression or death due to any cause, whichever comes first (up to approximately 79 months))