A Phase 1A/B Study To Evaluate The Safety And Tolerability Of EBC-129 As A Single Agent And In Combination With Pembrolizumab In Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 6
- 主要终点
- Part A, Part B, Part C and Part D- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs)
研究概览
简要总结
This study will assess the safety and tolerability of EBC-129 as a single agent and in combination with pembrolizumab in patients with advanced solid tumours
详细描述
This study is a prospective, open label study which is divided into 4 parts.
Part A will be dose escalation segment to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of EBC-129 monotherapy.
Part B will be dose escalation segment to identify the MTD and RP2D of EBC-129 in combination with pembrolizumab.
Part C (dose expansion cohort) will be performed in an expanded cohort of patients with advanced solid malignancies at the RP2D of EBC-129 as a monotherapy identified in the dose escalation segment, Part A.
Part D (Dose Fractionation Cohort) will be performed in patients with advanced solid malignancies with cancer indications that have shown preliminary clinical activity in Part C.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients ≥18 years (US) or ≥21 years (Singapore) old
- •Body weight within ≥40 kg - ≤100 kg during Parts A and B, and ≤120 kg during all other parts of the study
- •Demonstrated progression of a locally advanced unresectable or metastatic solid tumour with no alternative standard-of-care therapeutic option with a proven clinical benefit, or are intolerant to these therapies
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 for Part A and 0-1 for Parts B, C and D
- •Hepatic function and adequate renal function, as per protocol standard
- •Adequate bone marrow function as per protocol standard
排除标准
- •Unable or not willing to provide tumour tissue sample (from archival tissue or de-novo biopsy) unless if there is a significant risk for the patient to undergo biopsy
- •Has received investigational or anti-cancer therapy within 4 weeks (28 days) prior to starting study drug
- •Is receiving any concomitant anti-cancer therapy
- •Known severe hypersensitivity to E coli-derived products or filgrastim or peg-filgrastim and have significant allergies to such biological products
- •Has clinically active brain metastases
- •Has received prior radiation therapy
- •Has received prophylactic administration of haematopoietic colony stimulating factors within 4 weeks (28 days) prior to starting study drug
- •Patients concurrently using any strong P-glycoprotein (P-gp) inducers/inhibitors or strong cytochrome P3A (CYP3A) inhibitors within 14 days prior to the first dose of study drug or patients that use restricted or prohibited medications listed in the concomitant and other treatments section of the protocol
- •Pregnancy or breast feeding
- •For patients receiving pembrolizumab:
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Patients who, according to the currently approved Keytruda (pembrolizumab) US package insert (USPI)/summary of product characteristics, had an immune-related adverse event (irAE) for which permanent discontinuation is mandated (any Grade 4 event and Grade 3 events of pneumonitis, hepatitis, and nephritis). Also, patients without formal contraindication due to previous irAE with any immune checkpoint inhibitor (approved or investigational) are not eligible if the AE has not resolved to grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent per day) for ongoing management.
- •Patients with a history of pneumonitis/interstitial lung disease, patients who received live vaccines within 30 days of enrolment, and patients who discontinued prior immune checkpoint inhibitors due to Grade 2 myocarditis are excluded from enrolment into pembrolizumab-containing cohorts
- •Has had a major surgical procedure within 4 weeks (28 days) from starting the study drug
- •Patients with active or chronic corneal disorders, with other active ocular conditions requiring ongoing therapy or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy
- •Active infection including HIV, Hepatitis B or Hepatitis C
研究组 & 干预措施
Part A-Cohort 1
Patients will be administered Dose 1 of EBC-129 as a monotherapy.
干预措施: EBC-129 (Drug)
Part A-Cohort 2
Patients will be administered Dose 2 of EBC-129 as a monotherapy.
干预措施: EBC-129 (Drug)
Part A-Cohort 3
Patients will be administered Dose 3 of EBC-129 as a monotherapy.
干预措施: EBC-129 (Drug)
Part A-Cohort 4
Patients will be administered Dose 4 of EBC-129 as a monotherapy.
干预措施: EBC-129 (Drug)
Part A-Cohort 5
Patients will be administered Dose 5 of EBC-129 as a monotherapy.
干预措施: EBC-129 (Drug)
Part B
Patients will be administered three different dose levels of EBC-129 in combination with a fixed dose of pembrolizumab.
干预措施: EBC-129 (Drug)
Part B
Patients will be administered three different dose levels of EBC-129 in combination with a fixed dose of pembrolizumab.
干预措施: Pembrolizumab (Drug)
Part C
Patients will be administered the highest dose of EBC-129 as a monotherapy at the RP2D determined in Part A of the study.
干预措施: EBC-129 (Drug)
Part D: EBC-129
Patients will be administered EBC-129 as a monotherapy as per two-dose or three-dose per cycle regimen.
干预措施: EBC-129 (Drug)
结局指标
主要结局
Part A, Part B, Part C and Part D- Number of patients with serious adverse events (SAEs) and treatment emergent adverse events (TEAEs)
时间窗: From pre-screening (≥28 days from planned date of treatment i.e. Day 1) until end of study (EOS i.e., 30 days from last dose). Approximately 2 years
Part A, Part B and Part D- Determination of Maximum tolerated dose (MTD)
时间窗: Approximately 2 years
Part A, Part B and Part D- Determination of the Recommended Phase 2 dose (RP2D)
时间窗: Approximately 2 years
Part C- Objective response rate (ORR)
时间窗: Day 1 through 12 cycles (each cycle is 21 days)
The number (%) of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by investigator.
Part D- ORR
时间窗: Day 1 through 12 cycles (each cycle is 21 or 28 days)
The number (%) of patients with a best overall response of CR or PR per RECIST v1.1 as assessed by investigator.
次要结局
- Part A and Part B- ORR(Day 1 through 12 cycles (each cycle is 21 days))
- Part A, Part B, Part C and Part D- Disease control rate (DCR)(Approximately 3.3 years)
- Part A, Part B, Part C and Part D- Duration of Response (DoR)(Approximately 3.3 years)
- Part A, Part B, Part C and Part D- Time to Progression (TTP)(Approximately 3.3 years)
- Part A, Part B, Part C and Part D- Progression Free Survival (PFS)(Approximately 3.3 years)
- Part A, Part B, Part C and Part D- Overall Survival (OS)(Approximately 3.3 years)
- Part A, Part B, Part C and Part D- Maximum Plasma Concentration (Cmax) of EBC-129(Parts A, B and C: Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Trough Concentration (Ctrough) of EBC-129(Parts A, B and C: Cycle 1, 2, 3, and Cycle 4 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Area under the curve (AUC) of EBC-129(Parts A, B, and C: Cycle 1 and Cycle 2 (each cycle is 21 days); Part D: Cycle 1 (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Maximum plasma concentration at steady state (Cmax_ss) of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Trough concentration at steady state (Ctrough,ss) of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Area under the curve at steady state (AUC_ss) of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Accumulation ratios of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Time to maximum plasma concentration (Tmax) of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Half-life (t1/2) of EBC-129(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part B- Cmax of Pemrolizumab(Day 1 through 12 cycles (each cycle is 21 days))
- Part B- Ctrough of Pemrolizumab(Day 1 through 12 cycles (each cycle is 21 days))
- Part B- AUC of Pemrolizumab(Cycle 1 and 2 (each cycle is 21 days))
- Part B- Tmax of Pemrolizumab(Day 1 through 12 cycles (each cycle is 21 days))
- Part B- t1/2 of Pemrolizumab(Day 1 through 12 cycles (each cycle is 21 days))
- Part A, Part B, Part C and Part D- Number of patients with detectable Anti-drug antibodies (ADAs)(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A, Part B, Part C and Part D- Number of patients with neutralising antibodies(Parts A, B, and C: Day 1 through 12 cycles (each cycle is 21 days); Part D: Day 1 through 12 cycles (each cycle is 21 or 28 days))
- Part A- Comparison of tumour responses(Approximately 1.8 years)