A Phase 1 dose-escalation and expansion study of Avacta’s novel pre|CISION™ FAP-activated Doxorubicin prodrug
Avacta Group plc (AIM: AVCT), the developer of innovative cancer therapies and diagnostics based on its proprietary Affimer® and pre|CISION™ platforms, is pleased to announce that it has submitted a Clinical Trial Application (CTA) in the UK for a Phase 1, first-in-human, open label, dose-escalation and expansion study of its lead pre|CISION™ prodrug, AVA6000, in patients with locally advanced or metastatic selected solid tumours.
In AVA6000, Doxorubicin has been modified with Avacta’s pre|CISION™ chemistry which renders the modified drug inactive in the circulation until it enters the tumour micro-environment where it is activated by an enzyme called FAP (fibroblast activation protein) which is in high abundance in most solid tumours but not in healthy tissue such as the heart. AVA6000 has been shown in animal models to significantly increase the amount of active drug in a tumour compared with the heart and should thereby improve tolerability and achieve better clinical outcomes for patients.
The planned phase I study is 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 are 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.
The dose-escalation phase of the study, which will be carried out in 15-20 patients, is 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 will 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. This phase of study will comprise 45-60 patients in total.
If the AVA6000 study shows that the pre|CISION chemistry is effective in reducing systemic toxicity of Doxorubicin in humans, then it can be applied to a range of other established chemotherapies to improve their safety and efficacy. This would open up a pipeline of next generation chemotherapies for the Group with significant clinical and commercial value in a chemotherapy market that is expected to grow to $56 billion by 2024.
Alastair Smith, Chief Executive Officer of Avacta Group, commented: “I am absolutely delighted that we have achieved this landmark milestone for the pre|CISION platform and for the Group. I would express my gratitude to our clinical development team led by Neil Bell who recently joined the Group as Chief Development Officer, as well as our collaborators at Tufts University, who have worked tirelessly to meet a demanding timeline under difficult conditions during the pandemic.
The study will provide key information about the performance of the pre|CISION chemistry in humans that will underpin the value of a substantial pipeline of safer, next-generation chemotherapies. We have already begun development of pre|CISION 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.
We expect to receive feedback from the MHRA (Medicines and Healthcare products Regulatory Agency) on the Clinical Trial Application by February 2021. Dosing of first patients will commence when we have responded to that feedback and received approval to proceed. I look forward to updating the market on the detailed timing in due course.”
Neil Bell, Chief Development Officer of Avacta Group, commented: “I am delighted with the progress made since joining the company in July 2020. The AVA6000 CTA submission represents a major development milestone for the pre|CISION platform and the AVA6000 Doxorubicin pro-drug programme.
By utilising FAP activation, the pre|CISION platform enables an innovative and targeted chemotherapy system with the ability to deliver chemotherapies like Doxorubicin to the tumour microenvironment whilst limiting very severe and life-threatening toxicities in non-target tissues. pre|CISION has the potential to change current treatment paradigms for many chemotherapies which have not maximised their clinical utility.
We now look forward to working with the MHRA (Medicines and Healthcare products Regulatory Agency) to achieve approval for the CTA as early as possible and move AVA6000 into the clinic.”