Phase II trials next stop for AustCancer's Pentrix

Perth-based cancer vaccine developer Australian Cancer Technology is gearing up to begin Phase II trials of its Pentrix anti-cancer vaccine after it was shown to be well tolerated and elicit an immune response in all 14 patients with a range of metastatic cancers involved in the Phase Ib/IIa study.

The new data support the preliminary findings from the St Vincent's Hospital (Sydney) study, which were released in November, and pave the way for the larger trial, which is scheduled to begin in the second half of the year and designed to provide more evidence of Pentrix's efficacy.

AustCancer has yet to release full details of the planned Phase II trial -- these will come shortly -- but has indicated that patients included will be healthier than those in the previous trial, ideally having not yet undergone chemotherapy as this affects the immune system, and will have one cancer type rather than the range seen in the Phase Ib/IIa study, which included head and neck, colorectal, breast, non-small-cell lung, renal and prostate cancers.

The patients will also receive a more intense vaccination regimen over a longer time period than in the earlier trial, during which patients were given four consecutive monthly doses of Pentrix. Because this regimen produced immune responses that increased over the course of the injections it suggests that the immune system needs to be primed and that more frequent injections and a longer treatment period will be needed to induce an optimum immune response.

Initially, the Phase II trial will be run in Australia to answer some preliminary questions but it could develop into a multicentre trial with US participants, said AustCancer chief operating officer Julia Hill.

For the moment the company plans to proceed with the trial alone, using funds from the share placement in January and the recent sale of the last of the company's mining assets, Dr Hill said. But it is in preliminary discussions with a number of potential commercial partners for Pentrix and a partner may be on the cards in the future if this represents the best way forward for the company's shareholders, she says. According to managing director, Alistair Cowden, "Pentrix is virtually 'deal ready' now."

The company believes the vaccine may have blockbuster potential because it is designed to target up to half of all cancer patients by exploiting the most common genetic flaw implicated in the disease, a defective p53 tumour suppressor gene.

Pentrix is made up of a cocktail of peptides designed to induce the production of antibodies against tumour cells with a mutated p53 gene, earmarking the cancerous cells for destruction by killer T-cells. It is designed to overcome the body's inability to recognise tumours as foreign.

A pool of eight peptides was administered in the Phase Ib/IIa, of which three were found to produce a vaccine specific immune response. As a result, Pentrix will be re-formulated using only those three peptides shown to produce the strongest immunogenic response.

Dr Hill stressed that this in no way reduced the potential of the vaccine to target a wide range of cancers in which the p53 gene is defective. "We simply tested eight peptides because we didn't know which were the most relevant," she said.

Now that these have been identified, AustCancer has described the findings in a provisional patent that was lodged this week. A further patent application is also being prepared and will be submitted with the next three months.

The new results will be submitted for publication in an international peer-reviewed journal shortly and an abstract has been put in for the American Society of Clinical Oncology meeting in May.