Treatment With VBI-1901 Linked to Tumor Stabilization in Recurrent Gliobastoma Patients in Phase 1/2 Trial

Treatment With VBI-1901 Linked to Tumor Stabilization in Recurrent Gliobastoma Patients in Phase 1/2 Trial

Immune responses triggered by the investigational cancer vaccine VBI-1901 correlate with the stabilization of tumor size in patients with recurrent glioblastoma (GBM), a common and aggressive brain cancer, according to new results from a Phase 1/2a clinical trial.

The latest data from part A of the trial also validates blood biomarkers of anti-tumor immune responses that could be used to identify vaccine responders in part B, from which initial data are expected later this year, according to VBI Vaccines, the developer of VBI-1901.

The new updates were presented at the World Vaccine Congress Europe 2019, held recently in Barcelona, in a presentation titled “eVLPs as an Antigen Delivery & Immunomodulatory Platform in Cancer.”

“We are encouraged by the data we’ve seen to-date in Part A of the study, but also recognize that in early immuno-oncology clinical studies it is critical to establish a correlation between vaccine responses and observed tumor and clinical responses,” David E. Anderson, PhD, VBI’s chief scientific officer, who presented the results, said in a press release.

“This new immunologic and biomarker data further strengthens early activity observed thus far with VBI-1901 and we look forward to seeing the initial data from Part B of the study,” he added.

VBI-1901 is a GBM immunotherapy designed to stimulate the patient’s own immune system to identify and kill GBM cancer cells more effectively than the current standard care — surgical resection, followed by radiation and chemotherapy.

The vaccine elicits an immune response against two proteins — glycoprotein B (gB) and pp65 — present in a common virus, called cytomegalovirus (CMV). Glioblastoma tumors are very susceptible to infection by CMV, with more than 90% of tumors expressing proteins from the virus. By directing an immune response against CMV proteins, VBI-1901 could stimulate the immune system to attack GBM.

The potential vaccine uses VBI’s enveloped virus-like particle (eVLP) platform technology, which closely mimics the structure of viruses to help boost immune responses as well or even better than natural infections.

VBI-1901 is administered intradermally, or into the skin layer called the dermis, along with granulocyte-macrophage colony-stimulating factor, an adjuvant that promotes the function of dendritic cells, a type of white blood cell key to inducing specific immune responses.

VBI is currently testing the vaccine in adults with recurrent GBM in a multicenter, open-label Phase 1/2a trial (NCT03382977).

The trial has enrolled 18 patients (median age of 54 years; 12 men) with any number of prior recurrences in part A to define the safety, tolerability, and optimal dose of VBI-1901 — and is expected to enroll another 20 patients who have had a first recurrence in part B, which will extend testing of the optimal dose. Patients in both phases receive VBI-1901 every four weeks until clinical progression.

In July, VBI released data showing that the three doses tested — 0.4 micrograms (mcg), 2 mcg, and 10 mcg — were well-tolerated, with no safety signals observed.

New data now presented reveals that three of the six patients in the high-dose group (10 mcg) reached stable disease — tumors neither grew nor shrank — seen on magnetic resonance imaging (MRI) scans, compared with one of six and no patients in the low- and intermediate-dose groups.

Importantly, the tumor response matched a positive immunological response, with the expansion of circulating tumor-fighting T-cells, which specifically target both gB and pp65.

Conversely, immune cells known to suppress anti-tumor immunity, called T regulatory cells (Tregs), declined after VBI-1901 vaccination.

Survival data is still preliminary, but the three patients who have lived the longest without disease progression were vaccine responders — a median of 14.5 weeks versus six weeks for non-responders.

Biomarkers of an immune response against gB and pp65 will now be used to assess vaccine responses in patients enrolled in part B of the study.

The trial is underway at sites in Massachusetts and New York; more information is available here.

At the conference, Anderson also discussed proof-of-concept preclinical data that support a broader application of eVLP for cancer therapies.