A Study of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Diffuse Midline Glioma (DMG)

NCT04771897 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BXQ-350.AD
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the safety of BXQ-350 and determine the maximum tolerated dose (MTD) in children with newly diagnosed DIPG or DMG. All patients will receive BXQ-350 by intravenous (IV) infusion and radiation therapy. The study is divided into two parts: Part 1 will enroll patients at increasing dose levels of BXQ-350 in order to determine the MTD. Part 2 will enroll patients requiring a biopsy in order to assess BXQ-350 concentrations in the biopsied tumor.

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

DIPG; DMG; brain tumor; glioma

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0

  To determine the safety of BXQ-350 in children with newly diagnosed DIPG or DMG, as evidenced by the incidence of treatment emergent adverse events assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  12 months

• Part 1 - Maximum Tolerated Dose

  To determine the maximum tolerated dose (MTD) of BXQ-350, when given with radiation therapy, according to the investigational product (IP) related dose limiting toxicities (DLTs) in children with newly diagnosed DIPG or DMG.

  12 months

• Part 2 - BXQ-350 Concentration in Tumor Samples

  To determine the concentration of BXQ-350 in tumor samples as evidenced by laboratory analysis of excised tumor tissue for SapC levels (a component of BXQ-350).

  12 months

• Part 2 - BXQ-350 Concentration in Plasma Samples

  To determine the concentration of BXQ-350 in plasma samples as evidenced by laboratory analysis of plasma samples for SapC levels (a component of BXQ-350).

  12 months

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  12 months

• Overall Survival (OS)

  12 months

• Quality of Life (QoL)

  12 months

• Concentration of drug at steady state (Css)

  12 months

• Exposure to BXQ-350 - area under the curve (AUC)

  12 months

Study Arms (2)

Part 1 Dose Escalation: Safety and Tolerance

EXPERIMENTAL

Sequential cohorts of patients with newly diagnosed DIPG or DMG will be treated with escalating doses of BXQ-350 until the maximum tolerated dose (MTD) is established, or in the absence of a maximum administered dose (MAD), the highest planned dose level is reached and radiation therapy.

Drug: BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance

Part 2 BXQ-350 Tumor and Plasma Concentrations

EXPERIMENTAL

Newly diagnosed DIPG or DMG patients undergoing neurosurgical biopsy prior to receiving radiation therapy will receive BXQ-350 at the MTD established in Part 1, or the highest planned dose level, and radiation therapy. Excised tumor tissue and plasma samples will be evaluated for SapC levels and pharmacodynamic effects.

Drug: BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations

Interventions

BXQ-350 - Part 1 Dose Escalation: Safety and Tolerance DRUG

BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes (clinical formulation BXQ-350). During Part 1, BXQ-350 will be administered by intravenous (IV) infusion over twelve months.

Also known as: SapC-DOPS

Part 1 Dose Escalation: Safety and Tolerance

BXQ-350 - Part 2 BXQ-350 Tumor and Plasma Concentrations DRUG

BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes (clinical formulation BXQ-350). During Part 2, BXQ-350 will be administered by intravenous (IV) infusion over twelve months.

Also known as: SapC-DOPS

Part 2 BXQ-350 Tumor and Plasma Concentrations

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Each subject must meet the following criteria:
• Provide signed, written informed consent prior to the initiation of any study-specific procedures (consent from guardians for minor children and patient assent according to institution and Institutional Review Board (IRB) standards)
• Age ≥ 1 year of age and ≤ 30 years of age at the time of study entry
• Have radiographically suspected or histologically confirmed newly diagnosed DIPG or DMG with the following defining disease characteristics/features:
• Part 1 and Part 2:
• DIPG: radiographic imaging showing a diffuse expansion of the brainstem/pons by a tumor that is poorly defined but abnormally bright in signal on T2-weighted images and abnormally dark on T1-weighted images; contrast enhancement, when present, is typically mild; there may be some indication of necrosis, and the basilar artery is commonly engulfed by tumor.
• DMG: the same imaging characteristics as noted above for DIPG are present, but the lesion can extend superiorly up into the midbrain and thalami, and/or inferiorly to the medulla.
• In cases of disease that is not classic for DIPG or DMG, biopsy may be necessary in order to obtain histological confirmation of eligibility.
• Part 2: newly-diagnosed DIPG or DMG planning to undergo biopsy at the recommendation of the treating physician; to be considered evaluable for PK tissue concentration analysis, tumor samples must have at least 50% viable tumor cells with \<30% necrosis or hemorrhage as determined by the study neuropathologist
• If receiving glucocorticoid therapy: dexamethasone allowed with maximum allowable dose 16mg/day
• Have measurable or non-measurable disease per RANO criteria
• Have Lansky (age 1 - 15) / Karnofsky (age ≥ 16) Performance Score of ≥ 50% or Eastern Cooperative Oncology Group (ECOG) Performance Status (age ≥ 18) of 0 - 2
• Subjects unable to walk because of paralysis, but who can sit without assistance/restraint and control a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Have acceptable liver function defined as:
• Total serum bilirubin ≤ 1.5 x upper limit of normal for the study site (ULN) (in subjects with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN)

You may not qualify if:

• Subjects must not meet any of the following criteria:
• Have a concurrent or secondary malignancy
• Have a low-grade glioma (Grade II or less)
• Have received prior treatment with radiation, chemotherapy, anti-neoplastic, or investigational agents
• Have had major surgery other than a minor outpatient procedure within 28 days 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 poorly controlled hypertension despite the use of antihypertensive agents defined as blood pressure ≥95th percentile for age and weight or \>160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screening
• 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
• electrocardiogram (ECG) with QTc \>470 msec at screening
• echocardiogram with ejection fraction \<50% or a decrease in the left ventricular shortening fraction to \<27%
• Have a known history of Human Immunodeficiency Virus (HIV) seropositivity
• Have active (acute or chronic) or uncontrolled severe infections
• Have active poor wound healing (delayed healing, wound infection or fistula)

Sponsors & Collaborators

• Bexion Pharmaceuticals, Inc.: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (3)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45226, United States

Location

Nationwide Children's

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Brain Neoplasms; Glioma

Interventions

Drug Tolerance

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pharmacological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 25, 2021
• Study Start: May 24, 2021
• Primary Completion: October 4, 2024
• Study Completion: October 4, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)