Sina A. Jasim, MD, from the Mayo Clinic in Rochester, Minnesota, said in an email interview with Endocrinology Advisor that most patients respond well to surgery and radioactive iodine therapy (RAI), but other patients with differentiated thyroid cancer develop resistant disease, “which is progressive, symptomatic, and fatal.”
“VB-111 is a non-replicating, engineered AD-5 adenovirus that is selectively targeting tumor vasculature,” Dr Jasim said. “It utilizes a tissue- and condition-specific semi-artificial pre-pro-endothelin promoter to express a pro-apoptotic FAS-chimera transgene that is triggering apoptosis of angiogenic tumor vasculature in response to tumor necrosis factor stimulation.”
Dr Jasim, who presented the data at the 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association, and colleagues explained that VB-111 is a novel approach that could potentially address the need for additional effective therapies.
Their open-label, industry-sponsored, dose-escalating phase 2 study analyzed the safety and efficacy of patients with advanced RAI-refractory differentiated thyroid cancer, where the end point was progression-free survival at 6 months for 25% of patients.
The researchers divided 29 patients into 2 groups that received a single VB-111 infusion at a low dose (3 x 1012 viral particles) or a high dose (1 x 1013 viral particles) every 2 months until disease progression.
Regarding adverse effects, patients reported flu-like symptoms after VB-111 administration, which commonly resolved within less than 2 days.
Results revealed that 35% of patients in the high-dose group and 25% of patients in the low-dose group achieved progression-free survival at 6 months.
At 12 months, progression-free survival was 25% in the high-dose group vs 0% in the low-dose group, which may suggest dose-dependent disease stabilization. However, this finding did not reach statistical significance.
Current results indicate that median survival is 18 months in the low-dose group and 22 months in the high-dose group, although the data are not yet mature, according to Dr Jasim.
Dr Jasim and colleagues reported that 9 patients survived until final follow-up, with 8 patients (47%) in the high-dose group.
The research group is continuing to follow the surviving patients, who have all progressed past 18 months post-treatment.
This study is supported by VBL Therapeutics.
Jasim S. Poster 638: A Multi-cohort Phase II Trial Of VB-111 In
Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer. Presented at: 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association (ITC/ATA); Oct 18-23, 2015; Lake Buena Vista, Florida.