RE: Optimum Dose21 Dec 2022 09:24
The AVA6000 first in human trial has been restricted to the same dosing interval as for doxorubicin, 21 days. That was a sensible precaution for both patient welfare and Avacta's reputation.
If, as we all hope/suspect/believe, AVA6000 is highly/exquisitely targetted to the tumour microenvironment, then that restriction could/should be removed - possibly as soon as for the Phase 1b part of the trial. Consideration of what frequency and what dosage to use then come down to:
1. How far into the TME does AVA6000 get?
2. How susceptible to doxorubicin is the cancer cell during its lifecycle?
3. Do dead cancer cells block AVA6000's access within the TME and, if so, for how long?
Best case scenario would be total pervasion of the tumour by AVA6000, uneffected by the presence of dead cells, and susceptibility to doxorubicin throughout the cancer cell lifecycle
- High dose, short interval, few cycles.
Worst case would be only the outer part of the tumour being accessible, reduced further by the presence of dead cells, and the cancer cells only being susceptible to doxorubicin during part of their lifecycle.
- Lower dose, interval decided by how long it takes for the new cancer surface to be substantially clear of dead cells, several cycles.
Assumption here is that FAP is present throughout the tumour. If it is only at the growing edge of the tumour then an extra consideration is how far into the tumour does doxorubicin get?
Whilst all the questions about doxorubicin will already have answers due to the extensive studies done on it, the scheme set out here is very probably a gross simplification of the true situation.
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