Study to Evaluate the Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBl-1901 in Recurrent GBM Subjects
Featured Clinical Study
Study to Evaluate the Safety, Tolerability, and Optimal Dose of Candidate GBM Vaccine VBl-1901 in Recurrent GBM Subjects
Study Sponsor: VBI Vaccines Inc.
Study website: https://www.clinicaltrials.gov/study/NCT03382977
Study Number: NCT03382977
Tumor Type: Recurrent malignant glioblastoma, or GBM
Age Group: Adults
Gender: Female & Male
Study Phase: Phase 2b
Published Date: TBD
GENERAL OVERVIEW
Detailed Overview
Patients who receive VBl-1901 treatment will receive an intradermal (injection into the skin in the arm) immunization with VBl-1901 every 4 weeks until clinical disease progression.
Patients who receive the active comparator, or standard of care (carmustine or lomustine), will receive this treatment every 6 weeks until tumor progression or intolerable toxicity.
In earlier Phase 1/2a studies of VBl-1901 in patients experiencing recurrent malignant glioblastoma (GBM), the optimal dose was determined as well as factors that helped identify patients most likely to respond to treatment with VBl-1901. In the current Phase 2b study, eligible patients who are most likely to benefit from VBl-1901 will receive the optimal dose. This is a randomized study design, meaning approximately half of the patients will receive treatment with VBl-1901 while the other patients will receive already approved treatments (established standard of care). This study design is the best way to understand whether VBl-1901 has the potential to provide greater benefits than current treatments.
ELIGIBILITY
Inclusion Criteria
You may be eligible if:
- 18-70 years of age
- Confirmed WHO grade 4 glioblastoma
- Evidence of first tumor recurrence after an initial treatment regimen assessed by MRI of the brain.
- Karnofsky performance status (KPS) score of 70%. KPS is determined by the treating physician and describes the functional status of the patient.
- Corticosteroid (dexamethasone or equivalent) dosage of not more than 4mg daily that has been stable or decreasing for at least 5 days.
- No prior use of immune therapies, e.g. bevacizumab
Exclusion Criteria
You may not be eligible if:
- Tumor is present at multiple locations (multifocal disease).
- Radiotherapy treatment in the last 12 weeks.
- Corticosteroid treatment above 4mg daily
- Concurrent use of the Optune device
- Patients with a mutation in genes called IDH 1/2
- lf recurrent tumor was previously a lower grade glioma
STUDY DETAILS
Patient Participation Requirements
Patients will either receive a current standard-of-care treatment (carmustine, intravenously injected, or lomustine, orally administered) every 6 weeks until the clinical disease progresses or the patient experiences intolerable toxicity, or they will receive the study treatment, VBl-1901, administered via two equal intradermal injections in the inner forearm, once every 4 weeks until clinical progression occurs. Every 6 weeks patients will undergo an MRI to evaluate the response of the tumor to treatment. At the start of treatment and then every 3 months, a small amount of blood will be collected to evaluate the immune response to treatment.
The total number of visits depends on how long a patient remains on treatment. Generally, patient eligibility screening will take place within 2 weeks of starting treatment at which time a Physical Exam with vital signs, medical history, Neurological Exam, MRI, blood, and urine testing will take place to evaluate if the patient meets all Inclusion/Exclusion criteria. Every 6 weeks patients will undergo an MRI to evaluate the response of the tumor to treatment. At the start of treatment and then every 3 months, a small amount of blood will be collected to evaluate the immune response to treatment and to verify that the patient continues to meet inclusion/exclusion criteria. Once the patient has come off treatment, they will be requested to agree to long-term follow-up telephone calls but will no longer be requested to come for study visits.
Mechanism of Action
Cytomegalovirus (CMV) is a virus found in > 90% of glioblastomas (GBM), but is not found in healthy tissue around the tumor. VBI’s cancer vaccine candidate uses CMV as a foreign viral target within the tumor environment. VBl-1901 targets two proteins (antigens) found in CMV that are known to be highly potent targets for the immune system. By boosting CMV-specific immunity and directing it to CMV+ tumors, the aim is to eliminate or slow the tumor growth.
As multiple publications have determined using a variety of methods that greater than 90% of GBM tumors tested have been CMV-positive, accordingly, we do not require testing of tumor tissue for CMV positivity, which would lead to delays in enrollment/treatment for a rapidly growing recurrent tumor.
Possible Risks and Side Effects
Thus far, 28 patients have been treated with VBl-1901 used in this Phase 2b portion of the trial. No patients have discontinued treatment due to VBl-1901 side effects. The most common side effects are redness and/or itchiness at the injection sites, which typically disappear after 24 hours. Some patients have experienced a mild headache or fatigue, both of which go away within 24 hours.
Study Compensation
Reimbursement for attending study related visits may be available, please discuss this with the site staff.
Progress to Date
The FDA has granted both Fast Track Designation and Orphan Drug Designation to VBl-1901 in the recurrent setting, following encouraging Phase 1/2a study results. In the earlier phase 1/2a portion of the study, 44% (7/16) patients had evidence that tumor growth slowed or was reduced. This resulted in patients living approximately 5 months longer than expected with the standard of care treatment.
Study Data
The study is open at 10 locations in the United States, and enrollment is ongoing.
STUDY LOCATIONS & CONTACTS
California
University of California, Irvine
Irvine, California 92868
Manisha Dandekar, MSc, CCRP
714-456-8350
dandeka@hs.uci.edu
University of California, San Diego
La Jolla, California 92093
Sheila Medina-Torne, MPH
cancercto@ucsd.edu
University of California, Los Angeles
Neuro-Oncology Program
Los Angeles, California 90095
Emese Filka
Efilka@mednet.ucla.edu
Stanford University
Stanford, California 94305
Neuro Oncology
ecure-all-neuro-crc@lists.stanford.edu
Florida
Miami Cancer Institute
Miami, Florida 33176
Daylen L Santana
786-526-2000 x78528
DaylenS@baptisthealth.net
Illinois
Northwestern Memorial Hospital
251 East Huron Street
Chicago, IL 60611
Carlene Liana del Castillo
carlene.castillo@northwestern.edu
Massachusetts
Massachusetts General Hospital
Boston, Massachusetts 02114
Patrick Mostyn
617-726-2027
PatrickM_Mostyn@dfci.harvard.efu
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Amanda Spearman
617-632-6520
Amanda_Spearman@dfci.harvard.edu
New Jersey
The Valley Hospital – Neurosurgeons of
New Jersey
Ridgewood, New Jersey 07450
Robyn Chicherchia
201-634-5792
rchiche@valleyhealth.com
New York
The Neurological Institute of New York –
Columbia University
New York, New York 10032
Lisa Olmos
212-342-5162
lo2345@cumc.columbia.edu
Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee 37232
Neuro Oncology Team
800-811-8480
cip@vumc.org
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