First patient dosed in AVA6000 pro-Doxorubicin Phase I clinical trial

Avacta Group has dosed the first patient in its Phase I multicentre trial evaluating AVA6000, a novel pro-drug of Doxorubicin and the company’s first therapeutic based on its pre|CISION technology.

The pre|CISION platform incorporates a substrate that is specifically cleaved by the protease fibroblast activation protein alpha (FAPa), which is upregulated in most solid tumours and at low background levels in healthy tissue, providing an activation mechanism to ensure localised release of chemotherapeutic agents from their pro-drug form. By activating chemotoxins only within the tumour microenvironment, systemic exposure to healthy tissues is limited, improving the safety and therapeutic potential of these cancer therapies.

Anthracyclines such as Doxorubicin, a generic chemotherapy, are widely used as part of standard of care in several tumour types, but their use is limited by cumulative toxicity, particularly cardiotoxicity. Avacta’s pro-drug approach is reportedly designed to reduce the systemic exposure of healthy tissues to the active chemotherapy, leading to improved safety and therapeutic index, potentially resulting in improved dosing regimens, better efficacy and better outcomes for patients.

The AVA6000 study is a dose-escalation Phase I study in patients with locally advanced or metastatic selected solid tumours known to be FAP-positive. These cohorts will receive ascending doses of AVA6000 to determine the maximum tolerated dose and establish a recommended Phase II dose. The second part of the study is an expansion phase where patients receive AVA6000 to further evaluate the safety, tolerability and clinical activity at this recommended Phase II dose across selected tumour types.

The Phase I study is being initiated across a small group of UK oncology centres. The dose escalation phase is anticipated to complete by the second quarter of 2022, followed by completion of the dose expansion phase by the second quarter of 2023.

Dr Alastair Smith, Chief Executive Officer of Avacta Group, commented: “The initiation of the first in human Phase I clinical study for AVA6000 marks the transformation of Avacta Life Sciences into a clinical stage biopharmaceutical company. It is an outstanding achievement by the team, and we are extremely proud of what has been achieved since we established the collaboration with Professor William Bachovchin at Tufts University Medical School to develop the pre|CISION technology for tumour targeting.”

Neil Bell, Chief Development Officer of Avacta Life Sciences, commented: “The initiation of this AVA6000 Phase I trial is a significant and transformational milestone for Avacta . AVA6000 offers an opportunity to improve upon the current doxorubicin treatment paradigm for patients, either as a monotherapy or in combination. We look forward to the results from our AVA6000 first-in-human clinical trial as we strive to improve therapeutic index of doxorubicin for patients.”

Image credit: NationalCancer Institute

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