Study to Evaluate Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBI-1901 in Recurrent GBM Subjects

NCT03382977 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VBI-1901-01
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to assess the safety and tolerability of VBI-1901 in subjects with recurrent malignant gliomas (glioblastoma, or GBM).

Conditions

Glioblastoma Multiforme

Keywords

GBM; Glioblastoma; eVLP; VBI-1901; vaccine; immunotherapy; CMV; CNS; Brain; Cancer

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) occurring during Part A of the study

  Through 14 days after each study vaccination

• Occurrence of AEs during each treatment cycle

  Through 28 days after each study vaccination

Secondary Outcomes (9)

• Serum antibody immune response

  Baseline and 2 weeks after each dose of vaccine in Part A and Part B and every 3 months in Part C

• Cellular immune responses

  Baseline and 2 weeks after each dose of vaccine in Part A and Part B and every 3 months in Part C

• Progression free survival (PFS)

  From the date of first dose to date of progression or death, as well as at 6, 12, 18 and 24 months

• Overall survival (OS)

  6, 12, 18 and 24 months from date of first dose

• Median overall survival in Part A and Part B of the study

  Date of first dose to date of death from any cause, assessed up to 18 months

Study Arms (7)

Part A Dose Level 1

EXPERIMENTAL

VBI-1901 low dose (0.4 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Biological: VBI-1901

Part A Dose Level 2

EXPERIMENTAL

VBI-1901 intermediate dose (2 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Biological: VBI-1901

Part A Dose Level 3

EXPERIMENTAL

VBI-1901 high dose (10 μg pp65 content) vaccine formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal intradermal injections

Biological: VBI-1901

Part B GM-CSF Adjuvant

EXPERIMENTAL

VBI-1901 10 μg HCMV pp65 formulated with GM-CSF (200 μg) in 0.2 to 0.4 mL volume, given in two to four equal ID injections.

Biological: VBI-1901

Part B AS01B Adjuvant

EXPERIMENTAL

VBI-1901 10 μg HCMV pp65 formulated with AS01B (50 μg of QS-21 and 50 μg of MPL per dose) in 1.0 mL volume, given in one IM injection

Biological: VBI-1901

Part C VBI-1901 with GM-CSF Adjuvant

EXPERIMENTAL

VBI-1901 10 μg HCMV pp65 formulated with GM-CSF (200 μg) in 0.2 mL volume, given in two equal ID injections.

Biological: VBI-1901

Part C Standard of Care Treatment

ACTIVE COMPARATOR

Single-agent standard-of-care (SOC) treatment with either carmustine intravenously at a dose of 150 mg/m² or lomustine orally at a dose of 110 mg/m² (up to a maximum dose of 200 mg).

Drug: Carmustine; Drug: Lomustine

Interventions

VBI-1901 BIOLOGICAL

The vaccine is formulated with GM-CSF adjuvant and administered intradermally (ID) or with AS01B adjuvant and administered intramuscularly (IM) to patients with recurrent GBM.

Part A Dose Level 1; Part A Dose Level 2; Part A Dose Level 3; Part B AS01B Adjuvant; Part B GM-CSF Adjuvant; Part C VBI-1901 with GM-CSF Adjuvant

Carmustine DRUG

Treatment with carmustine intravenously at a dose of 150 mg/m² on Day 1 and every 6 weeks until the earlier of disease progression or intolerable toxicity.

Also known as: BiCNU

Part C Standard of Care Treatment

Lomustine DRUG

Treatment with lomustine given orally at a dose of 110 mg/m² (up to a maximum dose of 200 mg) on Day 1 and every 6 weeks until the earlier of disease progression or intolerable toxicity.

Also known as: Gleostine

Part C Standard of Care Treatment

Eligibility Criteria

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

You may qualify if:

• years of age
• Histologically confirmed WHO grade IV glioblastoma
• Unequivocal evidence of a tumor recurrence (any number of recurrences) or progression after an initial treatment regimen (prior to enrollment on this study) as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. An initial therapy requires surgery and radiation therapy, with or without temozolomide. In addition, alternate therapy (with or instead of temozolomide) is permitted as part of initial therapy.
• Recovery from the effects of surgery.
• Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days.
• Recovery from prior therapy toxicity defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia).
• Karnofsky performance status (KPS) score ≥ 70%.
• Adequate organ function, including the following:
• Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL
• Serum creatinine \< 1.5 × the upper limit of normal (ULN)
• Bilirubin \< 1.5 × ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × ULN
• Women of childbearing potential: negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment.
• Female subjects of childbearing potential and sexually active male subjects must agree to use an acceptable form of contraception for heterosexual activity (i.e., oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for \>30 days before Screening, during the study, and for 60 days after the last dose of study drug).
• Able and willing to comply with protocol requirements in the opinion of the Investigator, including being able to have an MRI.

You may not qualify if:

• Contrast-enhancing residual tumor that is associated with either diffuse sub-ependymal or leptomeningeal dissemination.
• Requirement of systemic corticosteroid therapy \> 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of VBI-1901 treatment.
• Evidence of HCMV viremia in serum of \> 18,200 (4.3Log10) IU/mL using FDA approved COBAS® AmpliPrep/COBAS® TaqMan® HCMV test (Roche).
• Surgical resection or major surgical procedure within 4 days prior to the start of VBI-1901, or stereotactic biopsy within 7 days prior to the start of VBI-1901.
• Active infection requiring intravenous antibiotics or antiviral.
• History of cancer (other than GBM or prostate) within the past 2 years that could negatively impact survival and/or potentially confound tumor response assessments within this study.
• Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B virus or Hepatitis C virus infections. Subjects with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Immunosuppressive agent within 4 weeks prior to the start of VBI-1901 treatment.
• Evidence of intra-tumoral or peri-tumoral hemorrhage on baseline, other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans.
• Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
• Lack of family or social support structure that would preclude continued participation in the study.
• PART B OPTIMAL DOSE
• years of age.
• Histologically confirmed WHO grade IV glioblastoma.
• Unequivocal evidence of a first tumor recurrence with measurable disease, of an area no greater than 400 mm2, which may include patients with resected first recurrence tumor after an initial treatment regimen (prior to enrollment on this study) consisting of surgical intervention (tumor resection) and radiation, with or without temozolomide chemotherapy (depending on the MGMT methylation status), as assessed by MRI of the brain with and without contrast within 30 days prior to the initiation of injections of VBI-1901. In addition, alternate chemotherapy (with or instead of temozolomide) is permitted as part of initial therapy.

Sponsors & Collaborators

• VBI Vaccines Inc.: lead

Study Sites (12)

University of California, Irvine

Irvine, California, 92868, United States

RECRUITING

University of California, San Diego

La Jolla, California, 92093, United States

RECRUITING

University of California, Los Angeles Neuro-Oncology Program

Los Angeles, California, 90095, United States

RECRUITING

Stanford

Stanford, California, 94305, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

The Valley Hospital - Neurosurgeons of New Jersey

Ridgewood, New Jersey, 07450, United States

RECRUITING

The Neurological Institute of New York Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Providence - Swedish Medical Center

Seattle, Washington, 98122, United States

TERMINATED

MeSH Terms

Conditions

Glioblastoma; Neoplasms

Interventions

Carmustine; Lomustine

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

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Officials

• Francisco Diaz-Mitoma, MD

  Variation Biotechnologies Inc.

  STUDY DIRECTOR

Central Study Contacts

Bebi Yassin-Rajkumar, MS

CONTACT

866-574-7034; BYassin-Rajkumar@vbivaccines.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None, open-label Allocation (FDAAA)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+ 3 Dose Escalation Therapeutic Vaccine: VBI-1901 The vaccine is formulated with GM-CSF adjuvant and administered intradermally (ID) or with AS01B adjuvant and administered intramuscularly (IM) to patients with recurrent GBM.

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: December 26, 2017
• Study Start: December 6, 2017
• Primary Completion: July 1, 2025
• Study Completion: August 1, 2025
• Last Updated: March 11, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

US (12)