A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of TAK-280 in Patients With Unresectable Locally Advanced or Metastatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 69
- 试验地点
- 41
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The main aim of this study is to find out the safety, tolerability, and effect of TAK- 280 in participants with unresectable, locally advanced or metastatic cancer who have experienced treatment failure or are intolerant to standard therapies.
Participants will be treated with TAK-280 for up to 14 treatment cycles. Each treatment cycle will be 28 days.
After the last dose of study drug, participants will be followed up for survival every 12 weeks for a total of 48 weeks.
详细描述
This study consists of 2 phases: Dose-escalation and cohort-expansion phase.
Dose-escalation phase:
The purpose of the dose-escalation phase is to generate data to characterize the initial safety and tolerability profile of TAK-280 and determine the 2 recommended doses for expansion (RDEs) of TAK-280 to be administered during the cohort-expansion phase.
Cohort-Expansion Phase:
The cohort expansion phase will be conducted in 3 indications. Only in 1 selected indication participants will be randomized 1:1 to receive either TAK-280 high dose or low dose. In the remaining 2 indications to be studied in the cohort-expansion phase, participants will receive only one dose level of TAK-280.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Age greater than or equal to (>=)18 years or >= the local legal age of majority, as applicable.
- •Criteria for disease state in dose escalation and cohort expansion.
- •Tumor histologies during dose escalation: Dose escalation will begin by initially enrolling participants with histologically or pathologically confirmed, unresectable, locally advanced or metastatic cancers.
- •Tumor histologies during cohort expansion: Participants will be eligible if they have histologically proven, unresectable, locally advanced or metastatic malignant neoplasms.
- •Eastern Cooperative Oncology Group performance status (less than or equal to [<=])
- •Measurable disease per RECIST V1.1 by investigator except for participants with mCRPC with bone metastases only (these participants are allowed in the study). Lesions in previously irradiated areas (or other local therapy) should not be selected as measurable/target lesions, unless treatment was >=6 months prior to start of treatment or there has been demonstrated progression with a clear margin to measure in that particular lesion.
排除标准
- •History of known autoimmune disease.
- •Major surgery or traumatic injury within 8 weeks before the first dose of TAK-
- •Unhealed wounds from surgery or injury.
- •Ongoing or active infection of Grade >=
- •Oxygen saturation less than (<) 92 percent (%) on room air at screening or during Cycle 1 Day 1 (C1D1) predose assessment.
- •Inflammatory process that has not resolved for >= 4 weeks before the first dose of study drug. Participants with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of their duration.
- •Vaccination with any live virus vaccine within 4 weeks or other vaccines within 2 weeks before the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
- •Known hypersensitivity to TAK-280 or any excipient.
研究组 & 干预措施
Dose-escalation Phase: TAK-280
Participants will receive TAK-280 intravenous (IV) infusion on Days 1, 8, 15, and 22 of a 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs.
干预措施: TAK-280 (Drug)
Cohort-expansion Phase: TAK-280 High or low Dose
Participants will receive either TAK-280 high or low dose in one selected indication and only one dose level of TAK-280 in the remaining indications as determined from the dose-escalation phase of the study in 28-day treatment cycle until disease progression, unacceptable toxicity, or withdrawal from study occurs.
干预措施: TAK-280 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From start of the initial dose up to Cycle 1 Day 28
DLT evaluation period is defined as the time between the initial dose of TAK-280 and Cycle 1 Day 28.
Number of Participants With Treatment- emergent Adverse Events (TEAEs)
时间窗: Up to approximately 37 months
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Cycle length=28 days)
DLTs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: From start of study drug administration up to follow-up (up to 37 weeks)
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE was defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of new anticancer therapy. AEs were evaluated according to NCI CTCAE, Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.
次要结局
- Area Under Plasma Concentration-Time Curve (AUC) of TAK- 280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Time to Reach Maximum Observed Plasma Concentration (tmax) of TAK-280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Disease Control Rate(Up to approximately 37 months)
- Percentage of Participants With mCRPC Having PSA Reductions of >= 50% up to 6 Months(Baseline up to 6 months)
- Total Clearance (CL) of TAK-280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Confirmed Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)(Up to approximately 37 months)
- Progression Free Survival (PFS)(From start of first dose to disease progression or death, whichever occurred first (up to approximately 37 months))
- Duration of PSA Response in Participants With mCRPC(Up to approximately 37 months)
- Percentage of Participants who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280(Cycle 1 to 5: pre-dose (Each cycle= 28 days))
- Percentage of Participants who Developed Neutralizing Antibody (NAb) Titers for TAK-280(Cycle 1 to 5: pre-dose (Each cycle= 28 days))
- Maximum Observed Plasma Concentration (Cmax) of TAK-280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Duration of Response (DOR) Based on RECIST V1.1(Up to approximately 37 months)
- Percentage of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response(Up to approximately 37 months)
- Time to PSA Progression in Participants With mCRPC(Up to approximately 37 months)
- Terminal Disposition Phase Half-Life (t1/2) of TAK-280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280(Pre-dose and at multiple time points post-dose on Days 1, 2, 3, 8, 15, 22 up to the end of treatment (Up to 14 months))
- Overall Survival (OS)(From start of first dose of study drug up to death (up to approximately 37 months))
- Maximum Observed Plasma Concentration (Cmax) of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last) of TAK- 280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Terminal Disposition Phase Half-Life (t1/2) of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Total Clearance (CL) of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Volume of Distribution at Steady State (Vss) After IV Administration of TAK-280(Cycles 1-7: Pre-dose and post-dose up to 48 hours on Days 1, 2, 3, 8, 15 and 22 (Cycle length= 28 days))
- Overall Response Rate (ORR)(Up to 37 weeks)
- Duration of Response (DOR)(Up to 37 weeks)
- Progression Free Survival (PFS)(Up to 37 weeks)
- Overall Survival (OS)(Up to 37 weeks)
- Disease Control Rate (DCR)(Up to 37 weeks)
- Number of Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Having Prostate-Specific Antigen (PSA) Response(Up to 37 weeks)
- Duration of PSA Response in Participants With mCRPC(Up to 37 weeks)
- Time to PSA Progression in Participants With mCRPC(Up to 37 weeks)
- Percentage of Participants With PSA Reductions of >=50% at 6 Months(At 6 months)
- Number of Participants Who Develop Positive Induced Antidrug Antibody (ADA) for TAK-280(Up to 37 weeks)
- Number of Participants Who Developed B7-H3 Targeted Neutralizing Antibodies (NAb) to TAK 280(Up to 37 weeks)
- Number of Participants Who Developed CD3 Targeted Neutralizing Antibodies to TAK 280(Up to 37 weeks)