CTIM-27 - Peripheral Biomarker Analysis of T cell-mediated Collagen Remodeling Correlates with Tumor Responses in a Phase IIa trial of vaccine immunotherapeutic candidate (VBI-1901)

Friday, November 17, 2023

7:30 PM – 9:30 PM PT

Location: Exhibit Hall A/B

Poster Presenter(s)

FI

Fabio M. Iwamoto

Division of Neuro-Oncology, New York-Presbyterian/Columbia University Medical Center
New York, New York, United States

Author(s)

NN

Neel Nissen

Nordic Bioscience
Herlev, Denmark
David A. Reardon

Center for Neuro-Oncology, Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Deborah A. Forst

Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School
Boston, Massachusetts, United States
Eudocia Q. Lee

Dana-Farber Cancer Institute, Boston, MA
Boston, Massachusetts, United States
TB

Tamara Berthoud

VBI Vaccines Inc.
Cambridge, Massachusetts, United States
CS

Catalina Soare

VBI Vaccines Inc.
Cambridge, Massachusetts, United States
FD

Francisco Diaz-Mitoma

VBI Vaccines Inc.
Ottawa, Ontario, Canada
DA

David E. Anderson

VBI Vaccines Inc.
Cambridge, Massachusetts, United States
Patrick Y. Wen

Dana-Farber Cancer Institute
Boston, Massachusetts, United States
NW

Nicholas Willumsen

Nordic Bioscience
Herlev, Denmark
MK

Morten Karsdal

Nordic Bioscience
Herlev, Denmark
Andrew B. Lassman

Columbia University Vagelos College of Physicians and Surgeons and New York Presbyterian Hospital
New York, New York, United States

Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4⁺ and CD8⁺ T cells are most frequently directed against the gB and pp65 antigens, respectively, which are immunogenic targets in a CMV-based GBM immunotherapeutic. First-recurrent GBM patients with KPS³70 received VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with GM-CSF intradermally (NCT03382977). Patients received VBI-1901 q4w, with serologic immune-monitoring q2w after each vaccination and surveillance brain MRI scans q6w. Among 16 patients treated with the highest (10µg dose) of VBI-1901, the mOS was 12.9 months with a 12-month OS rate of 62.5%. T cell-mediated collagen remodeling is necessary for T cell migration and activity. The peripheral C4G biomarker targets granzyme-B-cleaved type IV collagen, which is associated with T cell infiltration and has previously been shown to potentially identify recurrent GBM patients responding to nivolumab and bevacizumab. Here, C4G was measured in available plasma samples from patients with progressive disease (PD) (n=9), stable disease (SD) (n=5) or partial tumor responses (PR) (n=2) prior to (baseline) and after (cycle 1-4) treatment with VBI-1901. Although numerically lower in patients with PD, there were no differences in baseline levels of C4G among the groups. However, there were statistically significant increases in C4G levels in the 2 patients with PR both after 1^st/2^nd doses (p = 0.0324) and after 3^rd/4^th doses (p = 0.0027) of treatment (1^st/2^nd doses; PD: 7.6ng/mL, SD: 10.0ng/mL, PR: 21.0ng/mL. 3^rd/4^th doses; PD: 6.1ng/mL, SD: 8.5ng/mL, PR: 16.8ng/mL). On-going analyses are evaluating additional peripheral markers of tumor microenvironment (TME) remodeling. Evaluating the balance of immune infiltration vs. tumor cell growth in patients with brain tumors is challenging and these data suggest a means of assessing this dynamic using a peripheral biomarker. These data may be particularly useful in discerning pseudoprogression associated with T cell infiltration from tumor progression.