VBI-1901 Elicits Disease Control in Recurrent Glioblastoma

Treatment with the cancer vaccine immunotherapeutic VBI-1901 led to disease control in patients with recurrent glioblastoma (GBM), according to early response data from part C of a phase 1/2 trial (NCT03382977).^1,2

Findings presented at the 2024 World Vaccine Congress demonstrated that response-evaluable patients treated with VBI-1901 in part C of the trial (n = 5) experienced a disease control rate (DCR) of 40%, which was comprised of 2 patients who achieved stable disease (SD), defined as 12 weeks without tumor progression. Conversely, response-evaluable patients in the standard-of-care (SOC) arm (n = 6) experienced a DCR of 0%.2 Notably, all evaluable patients in the control arm experienced tumor progression and were removed from study protocol.¹

“In recurrent GBM, tumors typically double or triple in size within 6 weeks, with no effective treatments available to improve survival. Early indications from this ongoing study suggest tumor growth behavior in line with expectations for both the SOC arm and the VBI-1901 arm, based on positive data seen from the phase 1/2a study,” David E. Anderson, PhD, chief scientific officer of VBI Vaccines, stated in a news release.1 “While early, I am very excited by these results and hope to see the trends continue to confirm the results seen in earlier studies, where VBI-1901 improved median overall survival [OS] by [approximately] 5 months compared to historical controls—[approximately] 13 months vs [approximately] 8 months—and achieved a 44% DCR.”

VBI-1901 is a novel cancer vaccine immunotherapeutic designed using VBI’s enveloped virus-like particle technology. It is intended to target 2 highly immunogenic cytomegalovirus antigens: gB and pp65.¹

Previously reported data from parts A and B of the study showed that evaluable patients with recurrent GBM (n = 16) experienced a DCR of 44%, which included 2 patients who achieved a partial response and 5 patients who had SD. In this population, VBI-1901 elicited a median OS of 12.9 months, and the 12-month OS rate was 62.5%.²

Based on these prior data, the FDA granted fast track designation to VBI-1901 in June 2021 and orphan drug designation to the agent in June 2022.^3,4

In the part C, randomized, open-label portion of the study, investigators enrolled patients at least 18 years of age with histologically confirmed supratentorial grade IV GBM per 2016 WHO classification, or IDH wild-type or grade 4 GBM per 2021 WHO classification. Notably, patients with lower-grade GBM per 2021 WHO classification criteria with TERT promoter mutations, EGFR amplifications, and/or chromosome 7 gain/10 loss were not eligible.⁵

Other key inclusion criteria included unequivocal evidence of a first tumor recurrence with measurable disease of an area up to 600 mm2; 12 weeks since last radiotherapy treatment and/or 23 days since last chemotherapy prior to first dose of VBI-1901 or SOC treatment; a Karnofsky performance status of at least 70%; and adequate organ function.

Key exclusion criteria consisted of a history of receiving more than 1 line of prior chemotherapy; active infection requiring intravenous antibiotics or antivirals; a history of cancer—other than GBM or prostate cancer—within the past 2 years that has metastatic or local recurrence potential; and evidence of intra- or peri-tumoral hemorrhage on baseline MRI.

In the phase 2b, part C portion of the study, patients were randomly assigned to receive 10 µg of VBI-1901 plus granulocyte-macrophage colony-stimulating factor; or SOC consisting of carmustine or iomustine.²

Enrollment in part C is ongoing, where investigators aim to enroll 30 patients to each arm. Currently, 14 sites are actively recruiting patients, and additional interim data from the study are expected in the middle and end of 2024.

References

1. VBI Vaccines presents encouraging early tumor response data from randomized controlled phase 2b study of VBI-1901 in recurrent glioblastoma. News release. VBI Vaccines. April 3, 2024. Accessed April 3, 2024. https://www.vbivaccines.com/press-releases/vbi-vaccines-presents-encouraging-early-tumor-response-data-from-randomized-controlled-phase-2b-study-of-vbi-1901-in-recurrent-glioblastoma/
2. Anderson DE. Early tumor response data from the randomized, controlled phase 2b trial of VBI-1901 for the treatment of recurrent glioblastoma. Presented at: 2024 World Vaccine Congress Washington; April 1-4, 2024; Washington, DC. https://www.vbivaccines.com/wp-content/uploads/2024/04/WVC-2024-VBI-Vaccines-GBM-Presentation37.pdf
3. VBI Vaccines granted FDA fast track designation for VBI-1901 for the treatment of recurrent GBM. News release. VBI Vaccines. June 8, 2021. Accessed April 3, 2024. https://www.vbivaccines.com/press-releases/vbi-1901-gbm-fda-fast-track-designation/
4. VBI Vaccines receives U.S. FDA orphan drug designation for VBI-1901 for the treatment of glioblastoma. News release. VBI Vaccines. June 22, 2022. Accessed April 3, 2024. https://www.vbivaccines.com/press-releases/fda-orphan-drug-designation-vbi-1901-gbm/
5. Study to evaluate safety, tolerability, and optimal dose of candidate GBM vaccine VBI-1901 in recurrent GBM subjects. ClinicalTrials.gov. Updated March 15, 2024. Accessed April 3, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03382977