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
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
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.
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:
Inclusion Criteria:
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:
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:
Have acceptable coagulation parameters defined as:
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
Exclusion Criteria:
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:
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