A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent GBM

NCT02766699 | Completed Phase 1 FDA Drug

• 1 other identifier: ENG7
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the Cerebral EDV study is to determine the safety and tolerability of EGFR(V)-EDV-Dox in order to establish the best dose level to be used in future studies. The study will also examine the body's immune response to EGFR(V)-EDV-Dox and assess if it is effective in the treatment of patients with recurrent glioblastoma multiforme (GBM).

Conditions

Glioblastoma; Astrocytoma, Grade IV

Keywords

Astrocytoma, Grade IV; Doxorubicin; Glioblastoma; Neoplasms; Neoplasms by Site; Antineoplastic Agents; Drug Delivery Systems; Molecular Targeted Therapy; Nanoparticles; Disease Progression; Recurrence; Brain Neoplasms; Immunotherapy; Receptor, Epidermal Growth Factor; Antibodies, Bispecific

Outcome Measures

Primary Outcomes (1)

• Safety outcome measures

  Recording of adverse Events (AE's) and clinically significant changes in vital signs, physical and neurological examinations, cardiac tests, radiological imaging inc. CT scan (Day 27/28) and clinical laboratory tests.

  Safety measures will be conducted from Study Day 1 as per study schedule to safety follow-up visit 30 (+5 days) post last dose.

Secondary Outcomes (3)

• Efficacy outcome measure

  Screening, then post cycle (Days 50-56)

• Identification of a recommended Phase 2 dose (RP2D) of EGFR(V)-EDV-Dox in subjects with recurrent GBM

  DLT evaluable subjects are those who experience a DLT assessed within the first treatment cycle of Part 1 i.e.including up to 7 days after the final dose, days 1-50 of treatment.

• Overall survival outcome measure

  The number of days from the date of first administration of EGFR(V)-EDV-Dox to the date of death, regardless of cause up to 60 months.

Study Arms (1)

EGFR(V)-EDV-Dox

EXPERIMENTAL

EGFR(V)-EDV-Dox administered via 20 minute intravenous infusion once a week for seven weeks (1 Cycle). Subjects will receive one of two dose levels: 5 x 10\^9 or 8 x 10\^9. All subjects will undergo an adapted dose escalation regime in the first cycle of treatment. For subsequent cycles all doses will be administered at full strength (5x10\^9 or 8x10\^9 EGFR(V)-EDV-Dox). Subjects may receive further cycles of treatment if the tumor remains stable or is responding, and/or they are deriving clinical benefit from the therapy and are tolerating treatment.

Drug: EGFR(V)-EDV-Dox

Interventions

EGFR(V)-EDV-Dox DRUG

EGFR(V)-EDV-Dox using EnGeneIC EDV™ technology is a bacterially derived minicell which packages a toxic payload, Doxorubicin, into a 400 nm particle which targets specific cancer cells using bispecific antibodies (BsAb). BsAb-targeted, payload-packaged EDV nanocells only exit the leaky blood vessels associated with tumors and enter into the tumor microenvironment. The BsAb binds to the tumor cell-surface receptor, where the EDV is taken up, broken down within the cancer cell and releases the Doxorubicin. The residual EDVs that do not make it into the tumor microenvironment, are engulfed by cells of the immune system and since the EDVs are derived from bacteria, they carry potent immuno-stimulating components which appear to bypass the immuno-suppression caused by the tumor.

Also known as: EnGeneIC Dream Vector™, EnGeneIC Delivery Vehicle™

EGFR(V)-EDV-Dox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Karnofsky Performance Status (KPS) ≥ 60%.
• Life expectancy ≥ 3 months.
• Pathologically documented, and definitively diagnosed recurrent World Health Organization (WHO) Grade IV astrocytoma (GBM).
• Participant must have archived tumor tissue available from initial diagnosis or subsequent relapse(s) of Grade IV GBM for submission for central review at Investigational sites local laboratories.
• Recurrence or progression of disease (confirmed by MRI and measurable by RANO criteria) following receipt of standard of care therapy, which includes maximum safe surgical resection, standard adjuvant radiation/temozolomide treatment. Participants must have completed at least 21 days of temozolomide treatment in combination with radiation therapy to be considered to have received standard of care therapy.
• Participant has received no more than 1 other therapeutic regimen other than those listed above in (5).
• Participant may be receiving steroid therapy at time of enrollment (stable dose of ≤ 4 mg/day of dexamethasone or steroid equivalent).
• Ability to undergo MRI evaluation.
• Participant has ≥ 1 site of bi-dimensionally measurable disease measured using contrast enhanced MRI.
• Hematological function:
• White blood cell count (WBC) ≥ 3.0 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin \> 9 g/dL
• Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN)

You may not qualify if:

• History of central nervous system bleeding as defined by stroke or intraocular bleed within 6 months of enrollment.
• Evidence of acute intracranial / intra-tumoral hemorrhage, except for participants with stable grade 1 hemorrhage.
• History of coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association \> Class II), uncontrolled hypertension (systolic \> 160 mmHg or diastolic \> 100 mmHg) or cardiac arrhythmias requiring anti-arrrhythmic therapy.
• Clinically significant electrocardiogram (ECG) changes at enrollment which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome.
• Active infection requiring treatment.
• History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated with no evidence of disease for ≥ 2 years.
• Known positive test for human immunodeficiency virus infection (HIV), or active hepatitis B or hepatitis C infection.
• Receipt of therapies or procedures prior to first dose including:
• Radiation therapy within 6 months of Study Day 1 or has not recovered from the toxic effects of such therapy.
• Bevacizumab® or other anti-angiogenic therapy.
• Gliadel® Wafer (within 6 months of Study Day 1, or has not recovered from the toxic effects of such therapy).
• Immunotherapeutic agents, vaccines, or monoclonal antibody therapy (within 4 weeks of Study Day 1 or has not recovered from the toxic effects of such cancer therapy).
• Temozolomide or other chemotherapy (within 4 weeks of Study Day 1 or 6 weeks for nitrogen mustards, or has not recovered from the toxic effects of such cancer therapy).
• Anticoagulation therapy (within 7 days of Study Day 1), except low molecular weight heparins or low dose aspirin.
• Other investigational therapy (within 30 days of Study Day 1).

Sponsors & Collaborators

• Engeneic Pty Limited: lead
• Johns Hopkins University: collaborator

Study Sites (2)

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Lenox Hill Hospital, Northwell Health

New York, New York, 10075, United States

Location

MeSH Terms

Conditions

Glioblastoma; Neoplasms; Neoplasms by Site; Disease Progression; Recurrence; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Jennifer MacDiarmid, Ph.D

  Engeneic Pty Limited

  STUDY DIRECTOR

• Himanshu Brahmbhatt, Ph. D

  Engeneic Pty Limited

  STUDY DIRECTOR

• Gary L Gallia, M.D., Ph.D

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Stuart A Grossman, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation study

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 10, 2016
• Study Start: October 25, 2016
• Primary Completion: August 21, 2021
• Study Completion: March 30, 2022
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)