Phase 1, Dose-Escalation, Open-label, Safety and Pharmacokinetic, First in Human Study of BXQ-350 Administered as a Single Agent by Intravenous Infusion in Adult Patients With Advanced Solid Tumors and Recurrent High-Grade Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 4
- 主要终点
- Part 2-RECIST
研究概览
简要总结
The objective of this study is to characterize the safety profile and determine the maximum tolerate dose (MTD) of BXQ-350, when given as a single agent at escalating doses, according to the investigational product (IP) related dose-limiting toxicities (DLTs) in patients with advanced solid tumors. Secondarily to assess the preliminary antitumor activity of BXQ-350 in solid tumors and recurrent high grade gliomas.
详细描述
This is a first in man study of BXQ-350, a novel anti-neoplastic therapeutic agent composed of two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes. When both the components are assembled together forming stable SapC-DOPS nanovesicles (clinical formulation BXQ-350), the agent exhibits the propensity to enter the body and brain, target cells in the tumor mass, and induce cell death.
The study is divided into 3 parts:
- Dose Escalation Scheme Sequential cohorts of adult patients with advanced solid tumors and recurrent high-grade gliomas will be treated with escalating doses of BXQ-350 until the MTD is established, or in the absence of a MAD, the highest planned DL.
- During Part 2, patients with advanced solid tumors and recurrent high-grade gliomas will be enrolled and administered BXQ-350 at the MTD determined in Part 1 or at the highest planned DL, if the MAD is not reached.
- During Part 3, patients with either ependymoma, GI tumors , or advanced solid tumors other than HGG, will be enrolled and administered BXQ-350 at the 2.4 mg/kg dose level.
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
- •Each patient must meet the following criteria:
- •Provide signed, written informed consent prior to the initiation of any study-specific procedures
- •Have histologically or cytologically confirmed diagnosis of advanced solid tumor cancer (excluding lymphomas) for which there is no further standard therapy or when standard therapy is contraindicated. Patients with HGG must have shown unequivocal evidence for recurrence or progression by MRI scan or must have histologically proven tumor recurrence.
- •Patients with HGG: Have previously received radiotherapy and temozolomide
- •For patients with HGG and receiving glucocorticoid therapy, must be on stable or decreasing equivalent daily dose of glucocorticoids for 2 weeks (14 days) prior to dose assignment
- •Have measurable or non-measurable disease per RECIST 1.1 criteria for solid tumors and RANO criteria for HGG
- •Are males or females aged ≥ 18 years
- •Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 - 2
- •Have acceptable liver function defined as:
- •Total serum bilirubin ≤ 1.5 × upper limit of normal for the study site (ULN) (in patients with known Gilbert Syndrome, total bilirubin ≤ 3 × ULN, with direct bilirubin ≤ 1.5 × ULN)
- •Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 × ULN (if liver metastases are present, then ≤ 5 × ULN is allowed)
- •Serum albumin ≥ 3 g/dL
- •Have acceptable renal function defined as:
- •Serum creatinine ≤ 1.5 × ULN, OR calculated creatinine clearance ≥ 45 mL/min for patients with creatinine levels above 1.5 mg/dL
- •Have acceptable bone marrow function defined as:
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- •Platelet count ≥ 100,000 cells/mm3
- •Hemoglobin > 9.0 g/dL
- •Have acceptable coagulation parameters defined as:
- •International normalized ratio (INR) ≤ 2 × ULN
- •Activated partial thromboplastin time (aPTT) within normal limits
- •Have a negative serum pregnancy test result at screening (for females of child bearing potential (FCBP); not applicable to patients who are unable to become pregnant, including those with tubal ligation, bilateral oophorectomy and/or hysterectomy, post-menopausal is defined as > 12 months since last menstrual cycle)
- •FCBP and male patients whose sexual partner(s) are FCBP must agree to abstain from heterosexual activity or use a double barrier method of contraception (e.g., condom and occlusive cap with spermicide) or highly effective contraception (intrauterine device or system, established hormonal contraceptive methods on a stable dose from the time of the last menstrual cycle, or vasectomized partner with confirmed azoospermia) from the time of study entry to 1 month after the last day of treatment
排除标准
- •Patients must not meet any of the following criteria:
- •Have a concurrent malignancy or have had another malignancy within 1 year prior to initiation of screening (with the exception of adequately treated basal or squamous cell carcinoma, melanoma in situ, early-stage prostate cancer (T1a-cN0M0), ductal carcinoma in situ of the breast or cervical carcinoma in situ)
- •Patients with solid tumors: Have received anticancer therapies, including radiation therapy, cytotoxic agents, targeted agents or endocrine therapy within 2 weeks prior to dose assignment
- •Patients with HGG: Have received anticancer therapies including: radiation therapy to current site of disease within 12 weeks of dose assignment, targeted agent therapy within 2 weeks of dose assignment, nitrosoureas within 6 weeks of dose assignment, procarbazine within 3 weeks of dose assignment, or other cytotoxic agents within 4 weeks of dose assignment
- •Have not recovered from toxicity of prior therapy defined as a return to < grade 1 at the time of dose assignment, graded according to CTCAE v4.03 (excluding alopecia, neuropathy, and lymphopenia)
- •Have received prior treatment with any investigational drug within 4 weeks prior to dose assignment
- •Have had major surgery other than a minor outpatient procedure within 4 weeks prior to dose assignment or have not recovered from major side effects of the surgery if more than 4 weeks have elapsed since surgery
- •Have a history of cardiac dysfunction including:
- •Myocardial infarction within 6 months prior to initiation of screening
- •History of documented congestive heart failure (New York Heart Association functional classification III-IV) within 6 months prior to initiation of screening
- •Active cardiomyopathy
- •ECG with correctd QT interval (QTc) >450 msec in males or >470 msec in females at screening
- •Have a known history of HIV seropositivity
- •Are pregnant or nursing (lactating), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test
- •Have symptomatic brain metastases or leptomeningeal disease
- •Have active (acute or chronic) or uncontrolled severe infections
- •Have active poor wound healing (delayed healing, wound infection or fistula)
- •Have poorly controlled hypertension defined as blood pressure >160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screening
- •Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis, or gross hematuria) at screening
- •Have other concurrent severe and/or uncontrolled medical condition that would, in the site Investigator's judgment contraindicate the patient's participation in the clinical study
研究组 & 干预措施
Rising dose; safety and tolerance
Sequential cohorts of patients with advanced solid tumors and recurrent high-grade gliomas will be be treated with escalating doses of BXQ-350 until the MTD is established, or in the absence of a MAD, the highest planned DL is reached.
干预措施: BXQ-350 (Drug)
Solid tumor patients
Cohort of patients with advanced solid tumors administered BXQ-350 at the MTD determined in Part 1 or at the highest planned DL if the MAD is not reached.
干预措施: BXQ-350 (Drug)
Glioblastoma Multiforme patients
Cohort of patients with recurrent high-grade gliomas administered BXQ-350 at the MTD determined in Part 1 or at the highest planned DL if the MAD is not reached.
干预措施: BXQ-350 (Drug)
Gastrointestinal tumor patients
Cohort of patients with Gastrointestinal tumors as defined in the protocol and administered BXQ-350 at the 2.4 mg/kg dose level.
干预措施: BXQ-350 (Drug)
Ependymoma tumor patients
Cohort of patients with ependymoma administered BXQ-350 at the 2.4 mg/kg dose level.
干预措施: BXQ-350 (Drug)
Solid tumor patients other than HGG
Cohort of patients with advanced solid tumors other than HGG administered BXQ-350 at the 2.4 mg/kg dose level.
干预措施: BXQ-350 (Drug)
结局指标
主要结局
Part 2-RECIST
时间窗: 12 months
·To assess preliminary antitumor activity, defined as maximal radiological response during treatment using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1) criteria for solid tumors.
Part 1-MTD
时间窗: 12 months
· To determine the maximum tolerate dose (MTD) of BXQ-350, when given as a single agent at escalating doses, according to the investigational product (IP) related dose-limiting toxicities (DLTs) in patients with advanced solid tumors
Part 2-RANO
时间窗: 12 months
To assess preliminary antitumor activity, defined as maximal radiological response during treatment Revised Assessment in Neuro-Oncology (RANO) criteria for recurrent high grade glioma (HGG), of BXQ-350 given as a single agent at the MTD, or highest planned dose level (DL), in the absence of a Maximum Administered Dose (MAD).
Part 3 - RECIST
时间窗: 12 months
To assess preliminary antitumor activity, defined as maximal radiological response during treatment using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (v1.1) criteria for solid tumors
次要结局
- Part 2- Area under Curve (AUC)(12 months)
- Part 2-Cmax(12 months)
- Part 2-half life(12 months)
- Part 2-CL(12 months)
- Part 2-Progression-free survival (PFS-6)(12 months)
- Part 2-time to response(12 months)
- Part 2-duration of response(12 months)