Avacta Therapeutics (AIM:AVCT) reported early efficacy signals from its Phase 1a/1b trial of faridoxorubicin (AVA6000) in salivary gland cancers, with multiple confirmed responses and a decision to remove a lifetime doxorubicin exposure cap following cardiac-safety analyses.
At the recommended dose for expansion of 310 mg/m2, faridoxorubicin, a pre|CISION® tumor-activated version of doxorubicin from the clinical-stage company, showed lower rates of grade 3/4 toxicities than historical conventional doxorubicin despite being almost three times the conventional maximum tolerated dose of 75 mg/m2.
"Today's data further underscores our confidence in both our Gen One product faridoxorubicin (AVA6000) and our pre|CISION® technology to significantly improve treatment options for cancer patients," Christina Coughlin, Chief Executive Officer, said.
In the salivary gland cancer expansion cohort 38 patients were evaluable with four confirmed partial responses and nine minor responses, yielding a disease control rate of 92% (35/38).
Nine patients remain on treatment and a further 11 are in follow-up for disease progression.
Population PK modelling indicated AVA6000 removes the sharp systemic Cmax peaks seen with intravenous doxorubicin and results in higher clearance and a larger central volume of distribution for released doxorubicin.
Of 111 patients dosed to date there were no severe cardiac-toxicity events, only minimal LVEF changes, four patients (<4%) with significant LVEF reductions and no cardiomyopathy events of any grade.
An exposure-response analysis found no meaningful relationship between released doxorubicin exposure and LVEF change, and Health Authorities agreed the protocol lifetime maximum of 550 mg/m2 could be removed.
The study continues to enrol and Avacta plans to present further AVA6000 data at the BIO International Convention on June 22-25.
