Avacta Therapeutics (AIM: AVCT) reports 90% disease control rate in faridoxorubicin salivary gland cancer trial

Avacta Therapeutics plc (AIM: AVCT) has reported updated Phase 1b clinical data from its ongoing trial of faridoxorubicin (AVA6000), a tumor-activated doxorubicin conjugate for patients with salivary gland cancer (SGC). The results show sustained tumor shrinkage and a combined 90% disease control rate across both Phase 1a and 1b cohorts, reinforcing confidence in the company’s pre|CISION platform as a potential new standard in targeted chemotherapy delivery for solid tumors.

The announcement adds momentum to Avacta Therapeutics’ positioning in precision oncology as the first-in-class peptide drug conjugate (PDC) platform targeting fibroblast activation protein-alpha (FAP), an enzyme overexpressed in the tumor microenvironment. The platform’s differentiated mechanism of action could open treatment opportunities in previously chemo-resistant cancers.

How does faridoxorubicin differ from conventional chemotherapy in solid tumor treatment?

At the heart of Avacta Therapeutics’ strategy is its pre|CISION platform, which allows chemotherapeutic payloads to remain inactive in circulation and become activated only in FAP-rich tumor environments. In AVA6000, this mechanism is applied to doxorubicin, one of the most potent anthracycline agents in oncology but one that carries significant cardiotoxicity and systemic toxicity risks when delivered conventionally.

The updated Phase 1b data further supports the hypothesis that AVA6000 can selectively release the doxorubicin payload in the tumor, improving both safety and efficacy. Notably, among the 30 patients across both trial cohorts treated at a dose of 250 mg/m² and above, 27 experienced either partial responses, minor responses, or stable disease—translating into a 90% disease control rate.

The tumor shrinkage observed includes two confirmed partial responses and seven minor responses based on RECISTv1.1 criteria, highlighting durable anti-tumor activity in a cancer type with limited therapeutic options. Furthermore, the median progression-free survival (PFS) has not yet been reached in the Phase 1b cohort, with a median follow-up exceeding 15 weeks. Thirteen of nineteen patients remain on therapy at the data cutoff.

Why is salivary gland cancer a strategic entry point for AVA6000’s platform?

Salivary gland cancers make up a small but clinically significant subset of head and neck cancers, accounting for 6–8% of cases, with roughly 2,500 new diagnoses annually in the United States. The rarity of the disease, combined with a lack of standard systemic therapy in metastatic settings and low response rates to conventional chemotherapy, has created a clinically underserved segment.

The five-year survival rate in advanced SGC hovers around 42%, and patients often cycle through palliative treatments with poor long-term outcomes. This therapeutic vacuum creates a compelling rationale for targeted agents with both disease-modifying potential and tolerability advantages.

By demonstrating activity in both treatment-naïve and pretreated SGC patients, Avacta Therapeutics is signaling that its FAP-targeting PDC approach may bypass traditional resistance mechanisms associated with chemotherapy insensitivity in SGC. Seven of the Phase 1b patients had not received prior systemic therapy, yet early signals of tumor control were still evident, strengthening the argument for front-line use.

What does the Phase 1b dataset reveal about platform durability and translational potential?

From a translational medicine perspective, the most important aspect of this data readout may not be the tumor shrinkage rates alone but the validation of FAP as a reliable activation trigger for doxorubicin release—even in cases with low FAP expression.

This suggests that the pre|CISION technology could function consistently across diverse tumor types, provided FAP expression crosses the minimum threshold required for peptide cleavage. According to the company, optimal payload release was observed even at the lowest detectable levels of FAP, which expands the addressable market for other pipeline candidates leveraging the same platform.

The consistency of responses and durability across both cohorts further supports the idea that platform effect, not patient selection bias, is driving the observed efficacy. No signal loss or diminution of anti-tumor activity has been reported in the Phase 1b arm relative to Phase 1a, indicating reproducibility of response in a larger, slightly more heterogenous cohort.

How does faridoxorubicin compare to other FAP-targeting or tumor-activated agents?

While several programs in the industry target FAP for diagnostic or therapeutic purposes, including antibody-drug conjugates (ADCs) and radionuclide therapies, faridoxorubicin is one of the few agents employing a cleavable peptide strategy designed for cytotoxic drug activation. Companies such as Philogen and Telix Pharmaceuticals are also pursuing FAP as a theranostic target, but Avacta Therapeutics remains unique in positioning a doxorubicin conjugate in solid tumor indications like SGC.

Comparisons to ADC platforms are inevitable, but Avacta Therapeutics’ peptide-based approach offers manufacturing and safety profile advantages, potentially lowering barriers to combination use or outpatient administration. Importantly, the AVA6000 dataset shows efficacy even without the complex linker-stabilization chemistry that defines most ADCs, offering a simpler path to scale-up and regulatory clarity.

If AVA6000 continues to perform as expected through Phase 1b and beyond, it could eventually compete with or complement other tumor-activated chemotherapy platforms, including antibody-directed enzyme prodrugs (ADEPTs) and hypoxia-activated prodrugs that are still struggling to demonstrate consistent results in solid tumors.

What are the next clinical and regulatory steps for Avacta Therapeutics?

The company has confirmed that enrollment in the Phase 1b cohort will continue, with further data anticipated in the first half of 2026. With no dose-limiting toxicities or new safety signals reported thus far, it is likely that Avacta Therapeutics will soon pivot toward planning a Phase 2 expansion or a registrational pathway in SGC or broader FAP-expressing tumors.

The durability of response and ongoing progression-free survival observation will be critical to de-risking regulatory conversations around accelerated approval or orphan designation, particularly in a niche indication like SGC where therapeutic benchmarks are low.

From a capital allocation and pipeline development standpoint, Avacta Therapeutics’ near-term challenge will be choosing the next solid tumor settings to prioritize for its broader pre|CISION platform. Indications with high FAP expression and unmet need—such as pancreatic cancer, soft tissue sarcomas, or cholangiocarcinoma—could offer high strategic yield.

Investor sentiment around Avacta Therapeutics remains tightly coupled to platform validation. A strong Phase 1b showing, particularly if sustained over a longer follow-up horizon, would enhance the company’s standing for both capital market re-engagement and potential partnering discussions, especially if the SGC dataset can be extended to other rare or chemo-refractory solid tumors.

What are the key takeaways from Avacta Therapeutics’ AVA6000 Phase 1b update?

• Avacta Therapeutics reported a 90% disease control rate in its AVA6000 trial for salivary gland cancer, reinforcing the therapeutic potential of its pre|CISION platform.

• Faridoxorubicin showed durable tumor shrinkage in both treatment-naïve and pretreated patients, with no median progression-free survival reached yet in the Phase 1b cohort.

• The peptide drug conjugate selectively activates in the tumor microenvironment via FAP expression, potentially offering a safer, more effective alternative to conventional chemotherapy.

• Translational findings support consistent drug activation even at low FAP levels, broadening the platform’s applicability across solid tumors.

• The Phase 1b data confirm the reproducibility of response from Phase 1a, with no loss of efficacy or emergence of new safety signals.

• AVA6000 could challenge ADCs and other tumor-activated agents in niche solid tumor indications, particularly in cancers with poor chemotherapy response profiles.

• Further data expected in 1H 2026 could guide progression into Phase 2 or registrational studies and unlock potential for regulatory fast-tracking.

• Platform durability and target versatility remain central to investor confidence and potential strategic partnerships across the oncology ecosystem.