A Phase Ib2, multicenter, randomized, double-blind, placebo-controlled safety and efficacy study evaluating different regimens of the immunotherapeutic drug, Mobilan (M-VM3), in patients with prostate cancer.
Mobilan is a nanoparticle-formulated, recombinant non-replicating adenovirus immunotherapeutic drug that directs expression of both toll-like receptor 5 (TLR5) and a specific agonistic ligand, entolimod (which is a recombinant form of the natural TLR5 ligand, flagellin). The viral construct infects cells expressing the Coxsackie virus and adenovirus receptor (CAR), which has been shown in preclinical studies to be highly expressed in human prostatic tissue, including prostate cancer tissue. Upon infection, co-expression of both receptor and ligand in the same transfected cell triggers persistent autocrine stimulation of the nuclear factor-kappa B (NF-κB) signaling cascade. In a syngeneic mouse prostate cancer model, prostatic injection of Mobilan leads to activation of an innate immune response with infiltration of neutrophils and natural killer cells (NK) cells and induction of an adaptive immune response, comprising cytotoxic (cluster of differentiation \[CD\]8+) T cells. Necrotic changes in tumor cells were observed in Mobilan-treated animals with concomitant reductions in prostatic volume. Mobilan also show anti-metastatic activity in a surgical adjuvant mouse model of prostate cancer. This clinical trial is a Phase Ib double-blinded, randomized, placebo-controlled trial evaluating the efficacy, safety, and pharmacology of either 1 or 2 injections of Mobilan or placebo when administered as neoadjuvant therapy directly into the prostates of patients with newly diagnosed prostate cancer. All study subjects will receive 2 study drug injections administered 2 weeks apart and will be randomly allocated in a 1:1:1 ratio to 1 of the following 3 drug administration schedules: * Arm A: Mobilan on both Day 1 and on Day 15. * Arm B: Placebo on Day 1 and Mobilan on Day 15. * Arm C: Placebo on both Day 1 and Day 15 Subjects will subsequently undergo planned prostatectomy, ideally within 2 weeks following the final study drug injection and will remain under observation thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
Mobilan (M-VM3), innovative experimental drug based on non-replicate adenoviral delivery system consisting genomic vector coding TLR5-receptor and its ligand 502s.
5% infusion solution of dextrose (glucose)
Moscow State Budgetary Healthcare Institution "City Clinical Hospital № 57" of Moscow Healthcare Department
Moscow, Russia
Moscow State University of Medicine and Dentistry
Moscow, Russia
Federal State Budgetary Institution "Saint Petersburg Clinical Scientific and Practical Center for Special types of medical care (Oncological)"
Saint Petersburg, Russia
Federal State Budgetary Institution "Scientific Research Oncology Institute named after N.N. Petrov" of the Ministry of Health of the Russian Federation
Frequency and intensity of adverse events (according to CTCAE v 4.03 classification)
Time frame: Baseline to up to 45 days after the first drug administration
Counting of CD4+ and CD8+ cells in prostate biopsy and surgery samples
Using immunological assays
Time frame: Baseline to up to 45 days after the first drug administration
Change in total Prostate-specific antigen (PSA) level
Time frame: Baseline to up to 45 days after the first drug administration
Value of the Irani score of post-operative prostate tissue (if material is available for analysis)
Irani J (1997) scale include histological assessment of slide mounts obtained after operation as follow: Degree of immune cell infiltration: 0 - No inflammatory cells, 1 - Scattered inflammatory cell infiltrate within the stroma without lymphoid nodules, 2 - Nonconfluent lymphoid nodules, 3 - Large inflammatory areas with confluence of infiltrate
Time frame: On Day 30 after the first drug administration
Value of the Gleason score of post-operative prostate tissue (if material is available for analysis)
The Gleason grading system is used to evaluate the stage of prostate cancer using samples from biopsy or post- surgical samples as follow: 1 - The cancerous prostate closely resembles normal prostate tissue. 2 - The tissue still has well-formed glands, but they are larger and have more tissue between them. 3 - The tissue still has recognizable glands, but the cells are darker. 4 - The tissue has few recognizable glands. 5 - The tissue does not have any or only a few recognizable glands.
Time frame: On Day 30 after the first drug administration
Plasma concentration of inflammatory cytokines
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Saint Petersburg, Russia
Time frame: Baseline to up to 45 days after the first drug administration
Presence of protein 502s in blood plasma
Using ELISA assay
Time frame: Baseline to up to 45 days after the first drug administration
Presence of protein 502s in prostate biopsy and surgery samples
Using ELISA assay
Time frame: Baseline to up to 45 days after the first drug administration
Presence of protein TLR5 in prostate biopsy and surgery samples
Using ELISA assay
Time frame: Baseline to up to 45 days after the first drug administration