A Phase 1 Multiple Dose, Dose Escalation Trial of AEB1102 (Co-Arg1-PEG) in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 16
- 主要终点
- maximum tolerated dose
研究概览
简要总结
A first-in-human study of the safety of increasing dose levels of AEB1102 in patients with advanced cancers.
详细描述
In this phase 1 multiple dose, dose escalation study utilizing a classic 3+3 design. Sequential cohorts of patients will receive AEB1102 IV weekly at one of a series of increasing dose levels. Dose escalation will be dependent on the frequency of specific dose-limiting toxicities in the prior cohort of patients. The study will determine the maximum tolerated dose (MTD) of AEB1102, evaluate the safety profile of the compound, assess the pharmacokinetic profile of AEB1102, determine the effect of AEB1102 on blood arginine levels and evaluate the anti-tumor activity of AEB1102.
Following the determination of the MTD, additional cohorts of patients with uveal, cutaneous melanoma and small cell lung cancer will be enrolled and treated with AEB1102 at the MTD.
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
- •For patients participating in any part of the trial:
- •has an advanced solid tumor previously treated with, or inability to tolerate, standard therapy for the disease, or for which a standard therapy does not exist, and as such is considered a candidate for Phase 1 treatment
- •has adequate organ function: Hgb ≥9 g/dL; absolute neutrophil count (ANC) ≥ 1.5x109/L; plt ≥ 100,000/μL; AST and ALT < 2.5x ULN (< 5x ULN in patients with liver metastases); total bilirubin < 2.0 mg/dL; serum creatinine ≤ 1.5x ULN
- •ECOG performance score 0-2
- •For patients participating in any expansion group:
- •has measurable disease based on RECIST 1.1 as determined by the treating investigator. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •willing to consent for biopsy is strongly recommended but not mandatory
- •recovery of toxicities related to any prior treatments to at least Grade 1 by CTCAE v 4.
- •Exceptions are patients with adverse event(s) that are clinically nonsignificant and/or stable on supportive therapy.
- •For patients participating in specific expansion groups:
- •Cutaneous Melanoma:
- •unresectable, locally advanced or metastatic (AJCC stage IIIB, IIIC, or IV) cutaneous malignant melanoma
- •relapsed or progressive disease after or unable to tolerate at least one prior systemic anticancer regimen for metastatic disease involving immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4)
- •in tumors with a relevant BRAF mutation, relapsed, refactory, or unable to tolerate at least one prior systemic anticancer regimen for metastic disease involving a BRAF inhibitor
- •Uveal Melanoma:
- •uveal melanoma at metastic stage
- •Small Cell Lung Cancer:
- •extensive disease previously treated with, or inability to tolerate, platinum-based chemotherapy
排除标准
- •has primary CNS malignancy
- •history of untreated brain mets or leptomeningeal disease or spinal cord compression
- •effects of prior anticancer therapy recovered to grade < 2
- •known HIV
- •active infection
- •major surgery within 2 weeks
- •history of another malignancy within 2 years prior
研究组 & 干预措施
AEB1102 Dose Escalation Cohort 7
5 patients dosed at 0.27 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Expansion SCLC
13 SCLC patients dosed at 0.33 mg/kg
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 8
7 patients dosed at 0.40 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 9
7 patients dosed at 0.33 mg/kg until MTD determined MTD determined at 0.33 mg/kg
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Expansion Cutaneous
11 Cutaneous Melanoma patients dosed at 0.33 mg/kg
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Expansion Uveal
12 Uveal Melanoma patients dosed at 0.33 mg/kg
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 2
4 patients dosed at 0.02 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 4
4 patients dosed at 0.08 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 5
3 patients dosed at 0.12 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 6
4 patients dosed at 0.18 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 1
3 patients dosed at 0.01 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
AEB1102 Dose Escalation Cohort 3
4 patients dosed at 0.04 mg/kg until MTD determined
干预措施: Co-ArgI-PEG (Drug)
结局指标
主要结局
maximum tolerated dose
时间窗: 4 weeks
the dose level at which no more than 1/6 patients experiences dose-limiting toxicity
次要结局
- safety profile (changes in physical exam, laboratory measures, reported adverse events)(4 weeks +)