Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 288
- 试验地点
- 28
- 主要终点
- Part A-1 and A-2(escalations): Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
研究概览
简要总结
This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for expression of EphA2. The main goals of this study are to:
- Find the recommended dose(s) of BT5528 that can be given safely to participants alone and in combination with nivolumab
- Learn more about the side effects of BT5528
- Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer.
- Learn more about BT5528 therapy alone and in combination with nivolumab.
详细描述
BT5528 consists of a bicyclic peptide (Bicycle®) which binds to EphA2, and is covalently attached to a spacer and a protease cleavable peptide linker attached to MMAE.
The Phase I/II multi-center, open-label trial will evaluate BT5528 administered once-weekly as a single agent and in combination with nivolumab. The Phase I portion is a dose escalation primarily designed to assess the safety and tolerability of BT5528 and to determine recommended Phase II dose(s) (RP2D). Following selection of a recommended Phase II dose(s) (RP2D), a dose expansion portion will be initiated with the primary objective of evaluating the clinical activity of BT5528.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I - Dose escalation (BT5528)
Cohorts of participants will receive increasing doses of BT5528. It is expected that up to 72 participants will participate in this dose escalation arm.
干预措施: BT5528 (Drug)
Phase I - Dose escalation combination (BT5528 & nivolumab)
Cohorts of participants will receive increasing doses of BT5528 and a standard dose of nivolumab. It is expected that up to 24 participants will participate in this dose-escalation combination arm.
干预措施: BT5528 (Drug)
Phase I - Dose escalation combination (BT5528 & nivolumab)
Cohorts of participants will receive increasing doses of BT5528 and a standard dose of nivolumab. It is expected that up to 24 participants will participate in this dose-escalation combination arm.
干预措施: Nivolumab (Drug)
Phase II - Dose expansion 1 (BT5528)
A cohort of participants will receive the selected dose of BT5528 as a monotherapy. It is expected that up to 164 patients have solid tumors (Cohort 1: urothelial cancers, Cohort 2: ovarian cancer, Cohort 3: non-small cell lung cancer, Cohort 4: head and neck cancer, Cohort 5: triple-negative breast cancer, and Cohort 6: gastric/upper gastrointestinal cancer) historically known for high expression of EphA2 will participate in this dose-expansion arm, Cohort 7: urothelial MMAE exposed, Cohort 8: head and neck squamous cell carcinoma
干预措施: BT5528 (Drug)
结局指标
主要结局
Part A-1 and A-2(escalations): Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose
Safety reported as incidence of treatment-emergent adverse events
Part A-1 and A-2 (escalations): Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities from BT5528 treatment alone and in combination with nivolumab
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Maximum Tolerated Dose (MTD)
Part B: Objective response rate by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 tumor expression receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Objective Response Rate (ORR)
Part B: Duration of response by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Duration of Response (DOR)
Part B: Clinical benefit rate by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Clinical benefit rate
Part B: Time to tumor progression by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Time to Progression (TTP)
Part B: Progression-free survival by RECIST 1.1 in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks during study treatment)
Progression free survival (PFS)
Part B: PFS at 6 months by RECIST 1.1 in participants with solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Progression free survival (PFS)
Part B: Overall survival (OS) at 1 year in participants solid tumors historically known for high expression of EphA2 receiving BT5528 treatment
时间窗: From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent
Overall survival (OS)
次要结局
- Part B: The association between EphA2 expression level and objective response rate (ORR) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part B: The association between EphA2 expression level and duration of response (DOR) by RECIST 1.1 and per EphA2 expression in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part B: The association between EphA2 expression level and clinical benefit rate (CBR) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part B: The association between EphA2 expression level and time to tumor progression (TTP) per RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part B: The association between EphA2 expression level and progression-free survival (PFS) at 6 months by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part B: The association between EphA2 expression level and overall survival (OS) at 1 year by RECIST v1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 treatment(From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months))
- Part A-1 and A-2 (escalations): Objective response rate (ORR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part A-1 and A-2 (escalations): Duration of response (DOR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part A-1 and A-2 (escalations): Clinical benefit rate (CBR) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part A-1 and A-2 (escalations): Time to tumor progression (TTP) by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part A-1 and A-2 (escalations): Progression-free survival (PFS) time by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months)
- Part A-1 and A-2 (escalations): Progression free survival at 6 months by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months))
- Part A-1 and A-2 (escalations): Overall survival time at 12 months in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab(From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months)
- Part B: Determination of the number of participants with advanced solid tumors historically known for high expression of EphA2 receiving BT5528 with treatment-emergent adverse events(From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose)
- All parts: Determine the plasma concentrations of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab(From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months)
- All parts: Determine the plasma concentrations of MMAE in plasma from all participants taking BT5528 alone and in combination with nivolumab(From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months)
- All parts: Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT5528 alone and in combination with nivolumab(From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months)