Cavatak (coxsackievirus or CVA21) is an investigational virus-based therapy being developed by Viralytics. The therapy candidate is currently in clinical trials as a possible treatment of several cancers.

Cavatak consists of a live common cold virus, called coxsackievirus A21, which has the ability to attack and kill a wide range of cancer cells.

How Cavatak works

Cavatak works by attaching to a protein called intracellular adhesion molecule 1 (ICAM-1) and decay acceleration factor (DAF). Both ICAM-1 and DAF are found in excess on the surface of many cancer cells.

After attaching to ICAM-1 or DAF on a cell’s surface, the virus is able to enter the cancer cell, multiply, and eventually bursts (or lyse) the cell apart, releasing thousands of newly formed viral particles. The released  particles can then spread and target other cancer cells in the body, ultimately killing them as well. Cancer cell lysis also releases cancer cell proteins that are recognized by the body’s immune system, activating an anti-cancer immune response.

Cavatak in clinical trials

An open-labeled, multicenter Phase 2 study (NCT01227551), called the CALM study, was designed to evaluate the efficacy and safety of intratumoral (injected directly into a tumor) Cavatak in 57 patients with late-stage malignant melanoma. The results showed that Cavatak was well-tolerated, with both local and distant tumor responses.

A Phase 2 extension trial (NCT01636882) further investigated additional intratumoral injections of Cavatak in patients with late-stage melanoma, who had already demonstrated a response to Cavatak treatment in the initial CALM trial. Results showed that Cavatak treatment induced an increased infiltration of immune cells into tumors.

A two-part Phase 1 study (NCT02316171), called the CANON trial, evaluated the safety and anti-cancer activity of intravesicular (administered via a catheter directly into the bladder) Cavatak alone (part 1), and in combination with the low-dose chemotherapy mitomycin C (part 2). Patients enrolled had non-muscle invasive bladder cancer (NMIBC). Results showed that the combination treatment was well-tolerated, with an increased number of immune cells infiltrating tumor cells and evidence of anti-tumor activity.

An open-label, multicenter, dose-escalating Phase 1b study (NCT02043665), labeled STORM, is now investigating the safety and efficacy of intravenous (injected into the bloodstream as an infusion) of Cavatak alone and in combination with Keytruda (pembrolizumab) in patients with late-stage solid tumors (non-small cell lung cancer (NSCLC), castrate-resistant prostate cancer (CRPC), melanoma, and bladder cancer). Keytruda is a monoclonal antibody against a protein called programmed death receptor-1 (PD-1) that induces an immune response against tumors.

STORM consists of two parts. Part A, conducted in the U.K., tested Cavatak as a single therapy in people with NSCLC, CRPC, melanoma, and bladder cancer. Part B, now recruiting patients at sites in the U.S., Australia, and the U.K. (in collaboration with Merck) uses Cavatak in combination with Keytruda to potentially treat NSCLC and bladder cancer.

Part A has already been completed, while part B is currently recruiting patients; more information is available by clicking on the trial’s identification number. The combination of intravenous Cavatak and Keytruda has been generally well-tolerated.

An open-label Phase 1b study (NCT02307149) called MITCI, is also underway to evaluate the safety and anti-cancer activity of intratumoral Cavatak in combination with Yervoy (ipilimumab) in 26 patients with advanced melanoma. Yervoy is a monoclonal antibody against a protein called CTLA-4 (cytotoxic T-lymphocyte-associated protein 4). Preliminary study results found that the combination treatment was generally well-tolerated and showed long-lasting anti-cancer activity in local and distant tumors. This study is also enrolling at sites across the U.S.; more information is available by clicking on the trial’s identification number.

The Phase 1 CAPRA study (NCT02565992) is currently recruiting participants in California, New Jersey, and Ohio to evaluate the safety and tolerability of intratumoral Cavatak in combination with Keytruda in 30 patients with advanced melanoma. The study also aims to assess the anti-cancer activity of the combination. Interim results of the combo treatment in 15 patients demonstrate good tolerability, with tumor responses in 60 percent of these patients. Enrollment information is available by clicking on the trial’s identification number.

An open-label Phase 1b trial (NCT02824965) is currently recruiting participants in Australia to evaluate the safety and efficacy of intravenous Cavatak in combination with Keytruda  to treat patients with advanced NSCLC. The study will be conducted in two parts: part 1 will evaluate three ascending doses of Cavatak in combination with a fixed dose of Keytruda (200 mg). Part 2 will begin after a safe dose of Cavatak is determined. Enrollment information is available by clicking on the trial’s identification number.

***

Immuno-Oncology News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Erum Naqvi Editor
×
Erum Naqvi Editor