Avacta announced successful completion of fifth dose escalation in AVA6000 in its phase 1 clinical study and says a ‘very positive safety profile’ is under continuing observation despite this phase being completed successfully.
AVA6000 is a form of doxorubicin that has been chemically modified with Avacta’s pre|CISION platform designed to reduce systemic side effects by targeting the release of the active chemotherapy in tumor tissue.
The data continue to show a very favorable safety profile for the tumor targeted chemotherapy and several patients in cohort 5 and earlier cohorts remain on treatment as their disease has not progressed.
Despite the high dose level in the fifth cohort which is approximately 2.25 times a typical dose of doxorubicin, AVA6000 has continued to be well tolerated by patients with a marked reduction in the incidence and severity of the typical toxicities associated with the standard doxorubicin chemotherapy administration.
Both the positive safety and pharmacokinetic data emerging from the study support the potential support the potential differentiation of AVA6000 over doxorubicin. This includes higher dosing of the drug, more frequent dosing compared to doxorubicin – which is typically dosed every three weeks so patients can recover from the side-effects of treatment – and the ability to administer many more cycles of AVA6000 compared to doxorubicin.
Alastair Smith, chief executive of Avacta Group plc said: “The continued positive safety profile of AVA6000 at these dose levels compared with standard doxorubicin is remarkable. We are seeing a significant reduction in the incidence and severity of all doxorubicin side effects.”
He said analysis of the tumor biopsies to date also confirms that enough doxorubicin is being released in the tumor to have a therapeutic effect.
He added: “If even higher doses of AVA6000 are tolerated then this may make a significant difference to the outcomes for patients in the upcoming efficacy study.
Keen to progress
“We are keen to progress onto the Phase 1b efficacy study as soon as possible following completion of the dose finding Phase 1a study. The dose expansion Phase 1b study will provide an initial evaluation of efficacy and of the relative improvement in patient outcomes and quality of life of different dosing regimens of AVA6000 compared with the standard doxorubicin regimen.”
A total of 29 patients with a range of advanced and/or metastatic solid tumors have now been dosed at the clinical trial in sites in the UK and United States.
On the basis of the very favorable safety profile of AVA6000 in the study to date, the Safety Data Monitoring Committee (SDMC) has recommended continuation to the sixth dose cohort at 310 mg/m2 , which is equivalent to 2.7 times the standard dose of doxorubicin.
This continued dose escalation is aimed at identifying a maximum tolerated dose necessary to inform the dosing levels for the phase 1b and future studies.