A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of MB1707 in Patients With Advanced Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 主要终点
- Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)
研究概览
简要总结
The study will evaluate the pharmacokinetics (PK) and safety of a single intravenous (IV) dose of 0.3 mg/kg MB1707 in patients with advanced cancers.
详细描述
MB1707, paclitaxel (PTX) conjugated CXC chemokine receptor 4 (CXCR4) peptide antagonist, a peptide-drug conjugate (PDC), for the treatment of cancer. MB1707 is a potent CXCR4 antagonist which inhibits tumor growth and metastasis by blocking the stromal cell derived factor 1 (SDF-1, a.k.a. CXCL12)/CXCR4 signaling pathway. MB1707 contains a conjugated drug, paclitaxel. By specific binding to CXCR4 overexpressed by the tumor cells, MB1707 has a built-in targeted delivery mechanism.
The study will evaluate the PK and safety of a single intravenous (IV) dose of 0.3 mg/kg MB1707 in patients with advanced cancers.
Up to 6 patients will be enrolled.
Patients will be treated with a single intravenous (IV) dose of MB1707 over 3 hours on Day 1 only.
Patients will be pre-medicated with an antihistamine (eg, diphenhydramine), a corticosteroid (e.g., dexamethasone), and a H2 receptor antagonist (e.g., famotidine), within 30 to 60 minutes prior to infusion at doses per institutional guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 participants aged ≥18 years at the time of informed consent.
- •Patients who have previously received at least one line of standard systemic therapy for their advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the previous treatment eligible for treatment with a paclitaxel-based regimen.
- •Clinical Performance Status of Eastern Cooperative Oncology Group (ECOG) 0 or
- •Adequate bone marrow reserves
- •Adequate major organ system function
- •Female patients must not be pregnant or breastfeeding.
排除标准
- •Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
- •Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
- •Patients with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
- •Major surgery within 4 weeks prior to study entry.
- •Systemic anticancer therapy within 4 weeks prior to study entry
- •Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
- •History of severe immediate hypersensitivity reaction to paclitaxel
- •Active unstable or clinically significant medical condition
- •History of any major cardiovascular conditions within the past 6 months
- •Patients with known active, uncontrolled bacterial, fungal, or viral infection
研究组 & 干预措施
MB1707 Single Dose Phase 1
Phase 1 MB1707 given as a single intravenous (IV) dose of 0.3 mg/kg
干预措施: MB1707 (Drug)
结局指标
主要结局
Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)
时间窗: 2 days
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h) to the time of the last quantifiable concentration following dose administration
Area under the concentration-time curve extrapolated to infinity (AUC∞)
时间窗: 2 days
Determine Area under the MB1707 concentration-time curve from the time of dosing (0 h), extrapolated to infinity
Total body clearance (CL)
时间窗: 2 days
Determine total body clearance MB1707
Incidence of Adverse Events (AE) as characterized by type, frequency, severity (NCI CTCAE Version 5.0), timing, seriousness, and relationship to study therapy
时间窗: 14 days
Treatment-emergent AEs through 14 days after last protocol therapy will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) Version 14.0 (or higher) System Organ Class and preferred term. The incidences and percentages of participants experiencing each AE preferred term will be summarized with descriptive statistics. AEs will also be summarized by NCI CTCAE, Version 5.0, by grade and by causality (attribution to study treatment).
Peak Plasma Concentration (Cmax)
时间窗: 2 days
Determine Maximum observed MB1707 concentration from the time of dosing (0 h) to the time of the last quantifiable MB1707 concentration following dose administration
Half-life in plasma (t1/2)
时间窗: 2 days
Determine Apparent terminal phase half-life of MB1707
Time to Cmax (Tmax)
时间窗: 2 days
Determine Time of maximum observed MB1707 concentrations (post-dose)
Volume of distribution (VZ)
时间窗: 2 days
Determine Volume of distribution based on the terminal Phase of MB1707
次要结局
未报告次要终点