Avacta presents FOCUS-01 trial design and AVA6103 PDAC data at AACR

Avacta Therapeutics has presented preclinical data and the design of its FOCUS-01 Phase 1 trial for AVA6103, its lead next-generation peptide-drug conjugate (PDC), at the American Association for Cancer Research Conference on Pancreatic Cancer in San Diego. The presentation, delivered on 26 September 2026, focused on pancreatic ductal adenocarcinoma (PDAC), one of the most treatment-resistant tumour types in oncology.

AVA6103, also designated FAP-Exd, is built on Avacta's proprietary pre|CISION platform, which uses fibroblast activation protein (FAP) as a tumour-specific protease to concentrate the payload exatecan in the tumour microenvironment while limiting systemic exposure. In patient-derived xenograft mouse models of PDAC, the dose-dense, every-two-week (Q2W) regimen produced durable complete and partial responses across multiple models, with responses persisting for weeks after dosing stopped. Researchers also confirmed high FAP expression in PDAC and close proximity of FAP-expressing cancer-associated fibroblasts to both blood vessels and tumour cells, findings the company says directly support its mechanism of action.

Phase 1 progress and dosing rationale

The FOCUS-01 Phase 1a trial is a first-in-human, multicentre dose-escalation study enrolling patients with FAP-positive solid tumours, with PDAC patients assigned to the Q2W dose-intensive arm. Avacta says the PDC format enables more frequent dosing than conventional antibody-drug conjugates (ADCs) because the peptide does not accumulate as antibodies do, and because payload cleavage occurs within the tumour, substantially reducing peripheral exposure.

Preliminary safety and pharmacokinetic data from the first three dose levels, reported earlier in September, showed a favourable tolerability profile. AVA6103 was well tolerated at payload doses approximately 50% above the maximum tolerated dose of conventional exatecan, and PK profiles in patients were closely consistent with preclinical modelling. Enrolment has progressed to dose level 4, where the absolute payload dose exceeds double the MTD of exatecan alone and approaches the equivalent topoisomerase I inhibitor payload dose of Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo ADC approved in breast and gastric cancer. Chief executive Christina Coughlin said the company is now targeting an initial efficacy readout from FOCUS-01 in the first half of 2027.

Market context

PDAC carries a five-year survival rate of under 15% and remains one of the few major solid tumour types without a clearly dominant targeted therapy. The clinical success of ADCs, led by Enhertu, has drawn considerable investment toward next-generation conjugate formats that seek to improve the therapeutic window by reducing off-tumour toxicity. Several companies are pursuing FAP-directed and tumour stroma-targeting approaches, reflecting broader interest in exploiting the tumour microenvironment rather than solely surface antigens on cancer cells.

Avacta's PDC strategy distinguishes itself from ADCs by using a small-molecule peptide carrier rather than an antibody, which the company argues permits the dose-intensive scheduling that PDAC's aggressive biology demands. Whether that advantage translates to clinical benefit beyond the tolerability signal already reported will depend on the efficacy data expected in H1 2027. For investors in the AIM-listed company, that readout represents the most significant near-term catalyst for the programme.