Avacta submits clinical trial application for 'AVA6000' prodrug

Cancer therapy developer Avacta Group has submitted a clinical trial application in the UK for a phase 1 first-in-human open label dose-escalation and expansion study of its lead ‘preCISION’ prodrug, ‘AVA6000’, in patients with locally-advanced or metastatic selected solid tumours, it announced on Wednesday.

The AIM-traded firm said that in AVA6000, doxorubicin had been modified with Avacta's preCISION chemistry, which rendered the modified drug inactive in the circulation until it entered the tumour microenvironment, where it was activated by an enzyme called fibroblast activation protein (FAP), which was in high abundance in most solid tumours, but not in healthy tissue such as the heart.

It said AVA6000 had been shown in animal models to “significantly increase” the amount of active drug in a tumour compared with the heart, and should thus improve tolerability and achieve better clinical outcomes for patients.

The planned phase 1 study was a first-in-human, open-label, multi-centre study to be carried out in the UK in patients with locally-advanced or metastatic solid tumours which were known to be FAP-positive, including pancreatic, colorectal, breast, ovarian, bladder and non-small cell lung cancers, squamous cell carcinoma of the head and neck and soft-tissue sarcoma.

Avacta said the dose-escalation phase of the study, which would be carried out in between 15 and 20 patients, was designed to evaluate the safety of AVA6000 in humans and establish the appropriate dosing levels for the dose expansion phase of the study.

The dose expansion phase would consist of up to three studies in specific tumour types to further evaluate safety and tolerability, and to explore the anti-tumour activity of AVA6000 when administered as a monotherapy.

That phase of study would comprise between 45 and 60 patients in total.

If the AVA6000 study showed that the preCISION chemistry was effective in reducing systemic toxicity of doxorubicin in humans, then it could be applied to a range of other established chemotherapies to improve their safety and efficacy, Avacta claimed.

That, it said, would open up a pipeline of next generation chemotherapies for the group, with “significant” clinical and commercial value in a chemotherapy market that was expected to grow to $56bn by 2024.

“The study will provide key information about the performance of the preCISION chemistry in humans that will underpin the value of a substantial pipeline of safer, next-generation chemotherapies,” said chief executive officer Alastair Smith.

“We have already begun development of preCISION pro-drug forms of Velcade, Oxaliplatin and Paclitaxel so that we can rapidly accelerate one or more of these assets into the clinic when we see the first read-out from the AVA6000 trial approximately four months into the dose escalation phase.”

Smith said the company expected to receive feedback from the Medicines and Healthcare Products Regulatory Agency on the clinical trial application by February.

“Dosing of first patients will commence when we have responded to that feedback and received approval to proceed.”

At 0927 GMT, shares in Avacta Group were up 1.84% at 116.1p.