Pro-doxorubicin will advance to the fourth dose following a positive review of safety and tolerability.

Avacta Group – which develops oncology drugs based on its Affimer and pre|CISION platforms – has announced that the first-in-human phase 1 trial of AVA6000 Pro-doxorubicin will advance to the fourth dose cohort of patients, following a positive review of safety and tolerability data.

Avacta’s safety data monitoring committee (SDMC), comprised of clinicians currently recruiting patients, has completed its review of the safety data from the third cohort dosed with AVA6000 in the ongoing trial. Following the review, the SDMC has recommended that the clinical trial continues as planned and escalate to the next dose (200mg/m2).

AVA6000 is a novel form of doxorubicin that has been modified with Avacta’s pre|CISION fibroblast activation protein (FAP)-activated delivery platform to improve its safety and therapeutic index. Furthermore, the therapy has been designed to limit cell penetration of the drug – and, therefore, its cell-killing effect – until it is specifically activated by a FAP, which is in high concentration in many solid tumours compared with healthy tissues.

The resulting reduced exposure of healthy tissues to active doxorubicin has the potential to significantly increase its therapeutic index by reducing the incidence of adverse effects, including cardiotoxicity and myelosuppression.

Anthracyclines – such as doxorubicin – have a market size that is expected to grow to $1.38bn by 2024, and are widely used as part of the standard of care in several tumour types but their use is limited by cumulative dose toxicity associated with cardiomyopathy.

Dr Alastair Smith, chief executive officer of Avacta, explained: “We are very much encouraged by this recommendation from the SDMC to move onto the fourth dose cohort in our ongoing ALS-6000-101 phase 1 dose-escalation study. This very positive progress reflects the safety profile and tolerability demonstrated in patients enrolled in the study to date.”