AT SITC 2016

NATIONAL HARBOR, MD (FRONTLINE MEDICAL NEWS) – For patients with non-muscle invasive bladder cancer, intravesicular administration of an oncolytic virus was both feasible and safe, and in a small study was associated with at least one complete tumor response, investigators reported.

Instillation into the bladder of coxsackievirus A21 (CVA21; Cavatak), alone or in combination with low-dose mitomycin C, was associated with increases in immune cell filtrates and ramped-up expression of the programmed death-1 ligand (PD-L1) in the tumor microenvironment, reported Nicola Annels, PhD, a research fellow at the University of Surrey in England.

“Whilst the use of BCG [Bacille Calmette-Guerin] as an immunotherapy for non-muscle invasive bladder cancer has significantly improved disease-specific survival, the potential for serious side effects and local and systemic toxicity, together with the fact that there is a significant proportion of non-responding patients to BCG, highlights the need to develop future immune-based therapies to overcome these problems,” she said at the annual meeting of the Society for Immunotherapy of Cancer.

CVA21 is a proprietary formulation of coxsackievirus A21, a common cold virus. It targets intracellular adhesion molecule-1 (ICAM-1), and has been shown to have potent oncolytic activity against both non-muscle invasive bladder cancer (NMIBC) cell lines and ex vivo human bladder tumors. Delivering CVA21 with low-dose mitomycin C has been shown to enhance viral replication by increasing cell surface expression levels of ICAM-1, Dr. Annels noted.

In the stage I/II CANON study , the investigators studied the tolerability and safety of escalating doses of CVA21 alone or in combination with 10 mg mitomycin C in 16 patients with untreated NMIBC who were scheduled to undergo transurethral resection of bladder tumor (TURBT).

On serial cystoscopic photographs, the investigators saw evidence of anticancer activity including one complete response in one of three patients on CVA21 monotherapy at the highest of three doses, as well as virally-induced tumor inflammation.

Additional evidence of viral tumor targeting came from detection of secondary viral-load peaks in urine, and immunohistochemical analysis of tissues excised during TURBT, which tissue displayed tumor-specific viral replication and programmed cell death.

The authors also found that tissues treated with CVA21 showed upregulation of both interferon-response genes and immune checkpoint inhibitory genes compared with tissues from historical controls. This finding suggests that the antitumor effect of CVA21 might be enhanced by sequential administration of the virus followed by an immune checkpoint inhibitor, Dr. Annels said.

Patients tolerated the administration of CVA21 well, and there were no product-related adverse events greater than grade 1.

The activity observed thus “is likely to provide a strong signal in generating both a strong local and systemic anti-tumor response,” she said.

The study was funded by The Prostate Project, RingRose Foundation, Prostate Cancer UK, Topic of Cancer UK, Breast Cancer Campaign, the European Union, and Viralytics. Dr. Annels reported no conflicts of interest.