Australian immune-oncology company Imugene has recorded positive early signals from the first phase of its metastatic advanced solid tumour (MAST) clinical trial evaluating the safety and efficacy of its novel cancer-killing virus known as “Vaxinia” (CF33-hNIS).
The news comes hot on the heels of the company’s revelations last week that it had cleared the fourth cohort of the intravenous arm of its monotherapy dose-escalation study and had also passed evaluations for a second group of patients engaged in a combination study where Vaxinia is administered with the checkpoint inhibitor drug, pembrolizumab.
Also known as “Keytruda”, pembrolizumab is used to try and stop cancer cells from suppressing the immune system, allowing it to attack and kill the cancer cells.
Management says 34 patients have been dosed with Vaxinia during the dose-escalation phase, with 16 patients treated intratumorally and 18 patients intravenously as either monotherapy treatment or in combination with pembrolizumab. Of the 34 patients, 25 of them have entered the evaluation stage, with the remaining seven due to receive their first scan.
Encouragingly, one patient with bile duct cancer treated intravenously with a mid-dose has achieved a complete response with no recurrence in more than 200 days. Another patient has had a partial response and a further 16 patients have remained stable.
Early results from six patients with gastrointestinal cancers who received Vaxinia alone – including two with colorectal cancer, two bile duct, one pancreatic and one liver – showed positive treatment effects with a disease control rate of 75 per cent.
CF33 is a combination of genomic sequences from multiple vaccinia virus strains to generate a new, safer and more potent virus. When coupled with the human sodium-iodide symporter (hNIS) gene, which enables imaging to track the virus in vivo and mediate targeted radiotherapy, it is called Vaxinia.
The vaccinia virus has a short, well-characterised life cycle and spreads rapidly from cell to cell, but does not integrate into the host’s genome. It is highly cytolytic – which relates to the dissolution or destruction of a cell – for a broad range of tumour cell types and has the potential to act as both a gene therapy delivery vehicle and oncolytic agent.
Imugene’s phase-one trial kicked off in May last year, delivering a low dose of Vaxinia to patients with MAST who have undergone at least two standard-of-care cancer treatments. The company’s novel cancer-fighting oncolytic virus, developed at the world-renowned City of Hope National Cancer Institute in the United States, has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal trials.
Phase 1 trials are generally designed to look for safety, tolerability and early response signals to determine the optimal dose for further development. The early positive response data we are seeing at the mid-dose level in hard-to-treat bile duct cancer suggests that VAXINIA may be a potent anti-cancer drug as we interrogate higher dose levels. With no adverse safety signals, thus allowing us to dose higher, VAXINIA will have a very high therapeutic window which is valuable in oncology drug development. Imugene managing director and chief executive officer Leslie Chong
Bile duct cancers are notoriously difficult to treat and typically respond poorly to immunotherapy drugs. Early in the treatment process, tumours can exhibit signs of pseudo progression – a phenomenon in which the cancer initially appears to be growing, largely due to the cancer cells being infected by the virus followed by infiltration of cancer-fighting immune cells.
The phenomenon often leads to premature discontinuation of treatment owing to the false impression that the cancer is growing. Given time and continued treatment, the tumour can decrease in size as the therapy takes effect.
Owing to the early success in treating bile duct cancers, the company has committed to expanding the trial by treating an additional 10 patients with bile duct tumours.
Imugene’s phase-one CF33-hNIS trial is deep into its second year and the early signals are more than encouraging. The early success will no doubt provide a stronger glimmer of hope for the next two cohorts of patients preparing to enter the trial.
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