Avacta (LSE:AVCT) has presented the design of its FOCUS-01 Phase 1 clinical trial alongside new preclinical data for AVA6103 at the AACR Conference on Pancreatic Cancer.
AVA6103 is a FAP-enabled pre|CISION peptide-drug conjugate designed to deliver exatecan, a topoisomerase I inhibitor, within the tumour microenvironment.
The company is evaluating the drug in FAP-positive solid tumours, including pancreatic ductal adenocarcinoma, or PDAC.
Preclinical Studies Evaluate Two-Week Dosing
Preclinical studies using PDAC patient-derived xenograft models evaluated AVA6103 under a dose-dense regimen administered every two weeks.
Avacta reported tumour-targeted delivery of exatecan and complete and partial responses in the models, with responses persisting for several weeks after treatment ended.
Researchers also observed high FAP expression in the PDAC models and reported that FAP-positive fibroblasts were located close to blood vessels and tumour cells.
Avacta said these findings are consistent with the intended mechanism of its pre|CISION technology, which is designed to release its drug payload in FAP-rich tumour environments.
FOCUS-01 Trial Continues Dose Escalation
Avacta also presented early safety and pharmacokinetic findings from the first three dose levels of the Phase 1 FOCUS-01 trial.
According to the company, the results demonstrated proof of mechanism and AVA6103 was well tolerated at payload doses approximately 50% above the maximum tolerated dose of conventional exatecan.
Avacta said the pharmacokinetic profile observed to date was consistent with its preclinical modelling.
These findings are from an early-stage Phase 1 study, and further clinical data will be required to assess the safety and efficacy of AVA6103 in patients.
Enrolment Continues in Both Trial Arms
Patient enrolment is continuing across both arms of FOCUS-01, including a dose-intense every-two-week regimen for patients with PDAC.
Avacta said current dosing in this arm has reached a payload level exceeding twice the conventional maximum tolerated dose of exatecan and is approaching the payload exposure of Enhertu in breast cancer.
The trial is continuing to evaluate AVA6103 across increasing dose levels and dosing schedules.
About Avacta
Avacta Group plc, trading as Avacta Therapeutics, is a clinical-stage life sciences company developing targeted oncology treatments.
Its pre|CISION platform uses fibroblast activation protein to enable the release of drug payloads within the tumour microenvironment.
AVA6103 is an exatecan-based pre|CISION peptide-drug conjugate being developed for FAP-positive solid tumours, including pancreatic, cervical, breast, small cell lung, gastric and colorectal cancers.
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