Summary

Eligibility
for people ages 18-70 (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Timothy F Cloughesy, MD (ucla)

Description

Summary

The purpose of this study is to assess the safety and tolerability of VBI-1901 in subjects with Recurrent GBM.

Official Title

A Two-part, Phase I/IIA Dose-Escalation Study to Define the Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBI-1901 With Subsequent Extension of Optimal Dose in Recurrent GBM Subjects

Details

This is a two-part, dose-escalation study to define the safety, tolerability, and optimal dose level of candidate GBM vaccine VBI-1901 with subsequent extension of optimal dose level in recurrent GBM subjects. Subjects in the dose escalation (Part A of trial) as well as extension phase of the trial (Part B) will continue to receive vaccine every 4 weeks until tumor progression per iRANO criteria.

Keywords

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

Eligibility

For people ages 18-70

PART A DOSE ESCALATION

Inclusion Criteria: Part A Dose Escalation

  1. 18-70 years of age
  2. Histologically confirmed WHO grade IV glioblastoma
  3. 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.
  4. Recovery from the effects of surgery.
  5. Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days.
  6. Recovery from prior therapy toxicity defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia).
  7. Karnofsky performance status (KPS) score ≥ 70%.
  8. Adequate organ function, including the following:
  9. Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL
  10. Serum creatinine < 1.5 × the upper limit of normal (ULN)
  11. Bilirubin < 1.5 × ULN
  12. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN
  13. Women of childbearing potential: negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment.
  14. . 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).
  15. . Female subjects without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction.
  16. . Able and willing to comply with protocol requirements in the opinion of the Investigator, including being able to have an MRI.
  17. . Written consent has been obtained.
  18. . Tumor specimen available for central pathological review.

Exclusion Criteria: Part A Dose Escalation

  1. Contrast-enhancing residual tumor that is associated with either diffuse sub-ependymal or leptomeningeal dissemination.
  2. 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.
  3. Evidence of HCMV viremia in serum of > 18,200 (4.3Log10) IU/mL using FDA approved COBAS® AmpliPrep/COBAS® TaqMan® HCMV test (Roche).
  4. 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.
  5. Active infection requiring intravenous antibiotics or antiviral.
  6. 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.
  7. 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.
  8. Immunosuppressive agent within 4 weeks prior to the start of VBI-1901 treatment.
  9. 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.
  10. . Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
  11. . Lack of family or social support structure that would preclude continued participation in the study.

PART B OPTIMAL DOSE

Inclusion Criteria: Part B Optimal Dose

  1. 18-70 years of age.
  2. Histologically confirmed WHO grade IV glioblastoma.
  3. 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.
  4. At least 12 weeks since radiotherapy treatment and/or 23 days after chemotherapy prior to first dose of VBI-1901.
  5. Recovery from the effects of surgery.
  6. Corticosteroid (dexamethasone or equivalent) dosage ≤ 4mg daily that has been stable or decreasing for at least 5 days.
  7. Recovery from prior therapy toxicity, defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia).
  8. Karnofsky performance status (KPS) score ≥ 70%.
  9. Adequate organ function, including the following:
  10. Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL; absolute lymphocyte count ≥ 500/uL;
  11. Serum creatinine < 1.5 × the upper limit of normal (ULN);
  12. Bilirubin < 1.5 × ULN;
  13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN.
  14. . Women of childbearing potential must have a negative urine pregnancy test within 14 days prior to the start of VBI-1901 treatment.
  15. . 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).
  16. . Female subjects without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction.
  17. . Able and willing to comply with protocol requirements, in the opinion of the Investigator.
  18. . Written consent has been obtained.
  19. . Tumor specimen available for central pathological review.

Exclusion Criteria: Part B Optimal Dose

  1. Contrast-enhancing residual tumor that is any of the following:
  2. An area greater than 400mm2;
  3. Multi-focal (defined as two separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid-attenuated inversion recovery (FLAIR) or T2 sequences);
  4. Associated with either diffuse sub-ependymal or leptomeningeal dissemination.
  5. IDH1/2 has been proven to be mutated by IHC or PCR or if recurrent GBM was previously a lower grade glioma and wildtype IDH1/2 status has not been confirmed.
  6. 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.
  7. Evidence of HCMV viremia in plasma of >18,200 (4.3log10) IU/mL using FDA approved COBAS® AmpliPrep/COBAS® TaqMan® HCMV test (Roche).
  8. Prior treatment involving immunotherapy, including oncolytic viruses, therapeutic vaccination, or biologics (e.g. monoclonal antibodies, such as bevacizumab) presumed to have immunomodulatory effects.
  9. Surgical resection or major surgical procedure within 14 days prior to the start of VBI-1901, or stereotactic biopsy within 14 days prior to the start of VBI-1901.
  10. Radiation therapy, local therapy (except for surgical re-resection), or systemic therapy following first recurrence/progressive disease. Excluded local therapies include stereotactic radiation boost, implantation of carmustine biodegradable wafers (Gliadel), intratumoral or convection- enhanced delivery administered agents, etc.
  11. Concurrent therapy with Optune® or use within 1 week of start of treatment with VBI-1901.
  12. Active infection requiring intravenous antibiotics or antivirals.
  13. . History of cancer (other than GBM or prostate) within the past 2 years that has metastatic or local recurrence potential and could negatively impact survival and/or potentially confound tumor response assessments within this study.
  14. . 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.
  15. . Immunosuppressive agent within 4 weeks prior to the start of VBI-1901 treatment.
  16. . Any severe adverse event or allergy suspected or attributed to the shingles vaccines that contains AS01B components.
  17. . Evidence of intra- or peri-tumoral hemorrhage on baseline MRI scan, other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans.
  18. . Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
  19. . Lack of family or social support structure that would preclude continued participation in the study.

Locations

  • University of California, Los Angeles Neuro-Oncology Program accepting new patients
    Los Angeles California 90095 United States
  • The Neurological Institute of New York Columbia University Medical Center accepting new patients
    New York New York 10032 United States

Lead Scientist at UC Health

  • Timothy F Cloughesy, MD (ucla)
    Professor of Clinical , Neurology. Authored (or co-authored) 304 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
VBI Vaccines Inc.
ID
NCT03382977
Phase
Phase 1/2
Study Type
Interventional
Last Updated