A Phase 1/2A Trial of ENB 003 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 137
- 试验地点
- 5
- 主要终点
- Part A: Incidence of Treatment-Emergent Adverse Events of ENB003 in combination with pembrolizumab, as assessed by NCI CTCAE Version 5
研究概览
简要总结
First-in Human study evaluating the safety, tolerability and efficacy of ENB003 in combination with Pembrolizumab in solid tumors. The study is separated into two parts. Part A is a 3+3 dose escalation to define the recommended RP2D; this part will include metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer patients subjects, but other solid tumors will be allowed. Once the RP2D is selected, the study will be expanded into metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer subjects. A small number of sarcoma subjects will be included, as exploratory.
详细描述
Part A: Dose Escalation (with Run-in) A 7-day run-in period of ENB-003 monotherapy, will be administered to all Part A subjects on Days -7, -5 and -3, prior to initiating combination therapy with pembrolizumab at Day 1. ENB-003 will also be administered on Days 1, 3 and 5 in Cycle 1. In subsequent cycles, ENB-003 will be administered on Days 1, 3, 5, 8, 10, and 12 of alternate 21-day treatment cycles, starting with Cycle 3.
Dose escalation will follow a standard 3+3 design, with the following doses being administered during Part A:
- 150 µg ENB-003
- 300 µg ENB-003
- 500 µg ENB-003
- 750 µg ENB-003
- 1000 µg ENB-003 and 2000 µg ENB-003. For 2000 µg doses and above, ENB003 will be administered every 21 day cycle.
Pembrolizumab will be administered as 200 mg on Day 1 of each 21-day cycle in all Part A cohorts.
Part B: Dose Expansion Twelve (12) subjects with malignant melanoma, ovarian cancer, or pancreatic cancer will receive 1 x 21-day treatment cycle of ENB-003 at the recommended phase 2 dose (RP2D) selected in Part A + pembrolizumab. If dose limiting toxicities (DLT) occur in no more than 3 subjects , Part B will be expanded with an additional 27 subjects, plus 6 additional subjects with sarcoma. A review of efficacy will be conducted by a Data Safety Monitoring Board (DSMB) in Part B once 39 RP2D subjects (including 9 malignant melanoma subjects, 16 ovarian cancer subjects and 14 pancreatic cancer subjects) have completed their scheduled 12 week CT/MRI scans. Upon approval by the DSMB, a maximum of 64 further subjects will be treated at the RP2D.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（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
ENB003 750 ug + Pembrolizumab
750 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 750 ug + Pembrolizumab
750 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
ENB003 1000 ug + Pembrolizumab
1000 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 150 ug + Pembrolizumab
150 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 150 ug + Pembrolizumab
150 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
ENB003 300 ug + Pembrolizumab
300 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 300 ug + Pembrolizumab
300 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
ENB003 500 ug + Pembrolizumab
500 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 500 ug + Pembrolizumab
500 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
ENB003 1000 ug + Pembrolizumab
1000 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
ENB003 2000 ug + Pembrolizumab
2000 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg). In this treatment arm, ENB003 will be administered during each 21 day cycle, as opposed to every other cycle in early arms
干预措施: ENB003 (Drug)
ENB003 2000 ug + Pembrolizumab
2000 ug ENB003 will be administered in combination with a fixed dose of pembrolizumab (200mg). In this treatment arm, ENB003 will be administered during each 21 day cycle, as opposed to every other cycle in early arms
干预措施: Pembrolizumab (Drug)
ENB003 RP2D from dose escalation + Pembrolizumab
The recommended phase 2 dose (RP2D) of ENB003 will be selected from the dose escalation portion of the study and administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: ENB003 (Drug)
ENB003 RP2D from dose escalation + Pembrolizumab
The recommended phase 2 dose (RP2D) of ENB003 will be selected from the dose escalation portion of the study and administered in combination with a fixed dose of pembrolizumab (200mg)
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Part A: Incidence of Treatment-Emergent Adverse Events of ENB003 in combination with pembrolizumab, as assessed by NCI CTCAE Version 5
时间窗: assessed on every visit while subjects are in the study up to 2 years
Based on observed or reported AEs. AEs will be evaluated and classified according to NCI CTCAE Version 5.0
Part B: Efficacy of ENB003 in combination with pembrolizumab
时间窗: up to 2 years while subjects remain in the study
Pancreatic Cancer: • 6-months OS (evaluated in the context of ETBR expression) Note, these outcomes will be measured by tumor type and not in an aggregate as both the futility and final analysis are independently powered for each tumor type
次要结局
- pharmacokinetic (PK) of ENB-003-Cmax(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)
- pharmacokinetic (PK) of ENB-003-Tmax(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)
- pharmacokinetic (PK) of ENB-003-T1/2(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)
- pharmacokinetic (PK) of ENB-003-Vss(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)
- pharmacokinetic (PK) of ENB-003-CL(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)
- Exploratory: IHC assessment of ETBR(single sample taken between day 5-8)
- Exploratory: IHC assessment of PD-L1(single sample taken between day 5-8)
- Part B Efficacy Progression-free survival (PFS),(up to 2 years)
- Part B Efficacy: Duration of response(up to 2 years)
- Part B Efficacy: Time to progression(up to 2 years)
- Part B Efficacy: Overall survival(up to 2 years)
- pharmacokinetic (PK) of ENB-003-AUC(at 05,10,15, 20, 30 45, 60 and 90 minutes, 2 hours, 3 hours, 5 hours, and 8 hours after administration of the ENB003, on Days -7 and -5 during dose escalation and days 1 and 5 during dose expansion)