Avacta Reports AVA6103 Clinical Proof of Mechanism and Preclinical Results Against Enhertu

Avacta (LSE:AVCT) has reported clinical proof of mechanism for AVA6103, its investigational peptide-drug conjugate, following initial results from the ongoing Phase 1 FOCUS-01 trial in patients with solid tumours.

Early Phase 1a data from the first three dose levels showed limited haematological and gastrointestinal toxicity. The company reported that the administered payload dose reached approximately 50% above the maximum tolerated dose of conventional exatecan.

AVA6103 uses Avacta’s proprietary pre|CISION® platform, which is designed to enable controlled release of chemotherapy within tumours while limiting exposure elsewhere in the body.

Pharmacokinetic findings from the trial were consistent with the company’s preclinical models. The results showed rapid clearance of the conjugate from plasma, followed by prolonged, low-level release of exatecan and peptide.

According to Avacta, these findings support the proposed mechanism through which AVA6103 creates a drug reservoir within tumour tissue, allowing continued release of the chemotherapy payload.

The company also reported results from a preclinical study comparing AVA6103 with Enhertu®, a marketed HER2-targeting antibody-drug conjugate.

In a HER2-positive, FAP-positive gastric cancer model, AVA6103 demonstrated greater antitumour activity than Enhertu. The findings were obtained in a preclinical setting and do not establish comparative efficacy in patients.

Avacta said the results support further investigation of AVA6103’s potential for dose-dense treatment regimens and provide additional data for its ongoing discussions with prospective development partners.

The FOCUS-01 trial remains at an early clinical stage, with the initial findings covering the first three dose levels. Further clinical evaluation will be required to establish the drug’s safety, tolerability and efficacy.

Avacta is developing targeted oncology treatments using its pre|CISION® platform, which is designed to release chemotherapy payloads in tumour tissue through the activity of fibroblast activation protein (FAP).

The company’s development programme includes potential applications in colorectal, pancreatic, gastric, cervical and small cell lung cancers.

AVA6103 forms part of Avacta’s pipeline of peptide-drug conjugates intended to improve the delivery of chemotherapy agents, including exatecan, to solid tumours.