Treatment of recurrent glioblastoma with the investigational cancer vaccine VBI-1901 was well-tolerated and associated with stable disease in a subset of patients, according to findings of a Phase 1/2a trial.
The study, “Interim results of a phase I/IIa trial of a therapeutic CMV vaccine against recurrent glioblastoma (GBM),” was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. The full poster can be viewed here.
Because glioblastoma tumors are prone to infection by cytomagalovirus (CMV), VBI-1901 was designed to target two CMV proteins — glycoprotein B and pp65 — which are known to trigger strong immune responses. In this way, the cancer vaccine candidate is thought to stimulate the patient’s immune system to detect and kill glioblastoma cells more effectively than current standard of care.
VBI Vaccines’ VBI-1901 is administered intradermally, or within-the-skin, along with granulocyte-macrophage colony-stimulating factor, which is a molecule involved in the production and regulation of white blood cells and dendritic cells (type of immune cell).
The multi-center, open-label study (NCT03382977) included 18 patients (median age of 54 years; 12 men) in part A — intended to assess safety and tolerability — as well as part B, which will determine the optimal dose of VBI-1901. Treatment was given every four weeks until tumor progression. The patients had previously received treatment with radiotherapy, the chemotherapy temozolomide, or Opdivo (nivolumab, developed by Bristol-Myers Squibb).
The three doses tested — 0.4 µg, 2.0 µg, and 10.0 µg — were well-tolerated, with no safety signals observed. Moderate, severe, or life-threatening adverse events occurred in 66%, 22%, and 11% of participants, respectively, but none were related to VBI-1901.
Six patients showed CMV-specific immune responses to glycoprotein B and pp65. Median progression-free survival — the time without cancer progression — was longer among responders than non-responders (14.5 versus 6 weeks).
Also, three of six patients on the highest dose (10 µg) showed evidence of stable disease, as assessed by magnetic resonance imaging. In contrast, stable disease was observed in one patient of the low dose group and in none of the patients receiving the intermediate dose. Therefore, 10 µg was the selected dose for Part B, an extension phase expected to initiate enrollment by mid-2019 and include 10 more patients.
“The tumor responses seen in three of the six patients in the high-dose cohort are promising, with all three having immunologic responses to VBI-1901 as well,” David E. Anderson, PhD, VBI’s chief scientific officer, said in a press release.
He added that enrollment criteria in part B will be tighter “to ensure a more homogenous patient population that may better assess the potential correlation between immunogenicity and tumor and clinical responses to VBI-1901.”
Andrew B. Lassman, MD, a principal investigator of the study and chief of neuro-oncology at Columbia University Irving Medical Center, said that, although early, the data “are intriguing, yet of course require confirmation in later phase and additional trials.”
A therapy “that could demonstrate even some benefit would be incredibly meaningful for these patients and their families,” said Lassman, also the associate director for clinical infrastructure at Herbert Irving Comprehensive Cancer Center. “I look forward to seeing additional data from Part B of the study.”