VB-111 in Surgically Accessible Recurrent/Progressive GBM

NCT04406272 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-792
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is studying a new viral cancer therapy, ofranergene obadenovec (VB-111), for recurrent or progressive glioblastoma (GBM), a brain tumor that is growing or progressing despite earlier treatment.

Conditions

Glioblastoma; Recurrent Glioblastoma

Keywords

Glioblastoma; Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Tumor Infiltrating T Cell (TIL) Density

  TIL Density Analysis was not - and will not be - performed on study samples, therefore no data was generated for this study objective. * Tumor infiltrating T cell (TIL) density is defined as the number of T lymphocytes per nucleated cell, and calculated by detailed sequencing of recombined T cell receptor sequences obtained from the tumor specimen gDNA. * Plan had been to use a two-sample t-test with tumor size stratification to test the difference of tumor infiltrating T cell density between the two groups (Group A vs combined Group B+C).

  2 years

• # of Participants to Experience a Reportable SAE on Study

  AEs graded using CTCAE version 5.0 criteria. Safety will be assessed by quantifying the toxicities and grades experienced by participants who have received VB-111, including serious adverse events (SAEs) All participants who receive at least one dose of VB-111/placebo will be evaluable for toxicity from the time of their first treatment.

  2 years

Secondary Outcomes (2)

• 6-month Progression-free Survival (PFS-6)

  6 months

• Overall Survival (OS)

  Time from randomization until death from any cause; 37 months was the maximum time a participant remained in follow-up before passing away (10 pts), withdrawing consent (2 pts), being lost to follow-up (2 pts), or trial termination (1 pt).

Study Arms (3)

Before and After Surgery

EXPERIMENTAL

VB-111 will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovering from surgery (within 28-35 days after surgery), participants will receive intravenous VB-111 every 6 weeks. Participants evidencing disease progression may initiate bevacizumab at a pre-determined dose as needed for supportive care and will continue with VB-111 infusions every 6 weeks until tumor growth is evidenced a two consecutive time points.

Drug: VB11; Procedure: Surgery; Drug: Bevacizumab

After Surgery

EXPERIMENTAL

Placebo (IV solution with no medicine) will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovering from surgery (within 28-35 days after surgery), participants will receive intravenous VB-111 every 6 weeks. Participants evidencing disease progression may initiate bevacizumab at a pre-determined dose as needed for supportive care and will continue with VB-111 infusions every 6 weeks until tumor growth is evidenced a two consecutive time points.

Drug: VB11; Procedure: Surgery; Other: Placebo; Drug: Bevacizumab

After Surgery Standard of Care

EXPERIMENTAL

Placebo (IV solution with no medicine) will be administered intravenously at a pre-determined dose at 14-28 days prior to surgery. Upon recovery from surgery, participants will receive standard of care treatment every 6 weeks until tumor growth is evidenced a two consecutive time points.

Procedure: Surgery; Other: Placebo

Interventions

VB11 DRUG

Intravenously administered type of gene therapy that works by blocking the process of blood-vessel creation. Disrupting a cancer from growing blood vessels, might slow the growth of the cancer or shrink it.

Also known as: Ofranergene obadenovec

After Surgery; Before and After Surgery

Surgery PROCEDURE

Treatment of disease or injury by cutting, abrading, suturing, or otherwise physically changing body tissues and organs.

After Surgery; After Surgery Standard of Care; Before and After Surgery

Placebo OTHER

Intravenous solution that has no therapeutic effect, used as a control in testing investigational drug.

After Surgery; After Surgery Standard of Care

Bevacizumab DRUG

A type of antibody, Bevacizumab is intravenously administered and works by binding to and disrupting the vascular endothelial growth factor (VEGF). VEGF is a signal protein produced by cells that stimulates the formation of blood vessels. By disrupting VEGF, Bevacizumab helps to prevent the growth and maintenance of tumor blood vessels.

Also known as: Avastin

After Surgery; Before and After Surgery

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma).
• First or second progression of glioblastoma/gliosarcoma (according to RANO criteria) following standard of care treatment upon initial diagnosis with radiation.
• Measurable disease by RANO criteria at progression.
• The maximal tumor volume at baseline meets the following criteria as determined by a local site investigator or surgeon: Longest diameter ≤ 4CM.
• Surgically resectable disease at progression.
• An interval of the following durations prior to randomization:
• At least 28 days from prior surgical resection, or 7 days from stereotactic biopsy
• At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
• At least 23 days from prior chemotherapy
• At least 42 days from nitrosureas
• At least 42 days from other anti-tumor therapies (including vaccines)
• At least 28 days from any investigational agent NOTE: no wash-out period required from TTF.
• Corticosteroid use at or less than dexamethasone 2mg daily. Participants should be on a stable or decreasing dose for at least 7 days prior to randomization.
• Age ≥ 18 years on day of signing informed consent
• KPS ≥ 70% (see Appendix A)

You may not qualify if:

• Current or planned participation in a study of an investigational agent or using an investigational device.
• Has tumor primarily localized to the brainstem or spinal cord
• Has presence of diffuse leptomeningeal disease or extracranial disease.
• Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment
• Minor surgical procedure (e.g. stereotactic biopsy or shunt placement) within 7 days of first study treatment, placement of vascular access within 2 days of first study treatment
• Expected to have surgery other than the neurosurgical procedure intended for the GBM lesion during study treatment period
• Prior stereotactic radiotherapy (Note: those who have had biopsy proven tumor recurrence at a site of SRS treatment should be considered eligible if approved by the study central Investigator)
• Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.)
• Prior administration of the study drug VB-111
• Concomitant medication that may interfere with study results (e.g. immunosuppressive agents other than inhaled, topical or intra-articular steroids or a stable or decreasing dose of oral corticosteroids of up to \<2 mg/day dexamethasone equivalent)
• Known active second malignancy. Exceptions include non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Participants are not considered to have currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of stroke or transient ischemic attack within 6 months prior to randomization
• Evidence of CNS hemorrhage CTCAE grade 2 or above on screening MRI
• Active cardiac disease within 6 months prior to randomization (i.e. acute coronary syndrome, unstable angina, New York Heart Association grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Vascular Biogenics Ltd. operating as VBL Therapeutics: collaborator

Study Sites (4)

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

UT Health San Antonio MD Anderson Cancer Center (Mays Cancer Center)

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute (HCI), University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Surgical Procedures, Operative; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Patrick Y. Wen, MD
• Organization: Dana-Farber Cancer Institute

patrick_wen@dfci.harvard.edu

617-632-2166

Study Officials

• Patrick Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 28, 2020
• Study Start: August 1, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)