Is Avacta Therapeutics changing the rules of chemotherapy? Inside the Phase 1a findings that impressed ESMO

Avacta Therapeutics plc (AIM: AVCT) presented standout Phase 1a clinical trial results for its tumor-activated chemotherapy candidate faridoxorubicin (AVA6000) at the 2025 European Society of Medical Oncology (ESMO) Annual Congress in Berlin. The British clinical-stage biopharmaceutical company reported no maximum tolerated dose even at 385 mg/m²—roughly four times the standard doxorubicin dose—alongside a 91 percent disease control rate in salivary gland cancer patients. Crucially, no severe cardiac toxicity was observed, even at cumulative exposures up to 550 mg/m², underscoring the platform’s potential to safely deliver higher-intensity chemotherapy through its proprietary pre|CISION delivery mechanism.

Faridoxorubicin, which is being developed under Avacta Therapeutics’ proprietary pre|CISION platform, is a FAP-activated prodrug of doxorubicin. Its design aims to selectively release the active chemotherapeutic in the tumor microenvironment while shielding healthy tissues from the drug’s toxic effects. These newly presented data validate the company’s hypothesis that the pre|CISION platform could address one of the longest-standing limitations of anthracycline chemotherapy—systemic toxicity—without compromising anti-tumor efficacy.

The October 19 data release follows previous early-stage findings disclosed at the AACR Annual Meeting in April and comes at a moment when targeted chemotherapy and prodrug delivery systems are garnering renewed interest from institutional investors and oncology researchers seeking scalable alternatives to traditional cytotoxic regimens.

What do Avacta Therapeutics’ Phase 1a results show about the safety and efficacy of faridoxorubicin?

Across both the three-week and two-week dosing regimens in the Phase 1a trial, faridoxorubicin showed a consistently favorable safety profile in 63 patients. No maximum tolerated dose was identified, despite escalating doses up to 385 mg/m², which is roughly four times the standard administration level of conventional doxorubicin. Even at a cumulative exposure of 550 mg/m², which historically increases the risk of cardiac toxicity, no severe cardiac events were observed in any patient treated.

In the salivary gland cancer cohort of 11 patients who received 250 mg/m² or more, faridoxorubicin achieved a disease control rate of 91 percent. Several confirmed partial and minor responses were recorded, and notably, median progression-free survival (PFS) has not yet been reached. The reported median follow-up duration was 41 weeks, with Kaplan-Meier projections extending up to 51 weeks. This contrasts favorably with benchmark PFS data in this population, which range from 3.5 to 4 months in pretreated cohorts and 4 to 6.5 months in first-line settings based on data presented by the European Organisation for Research and Treatment of Cancer in 2024.

In patients with soft tissue sarcomas, a similar pattern emerged. Among 17 evaluable patients, responses were observed across several dose levels, including one partial response at the lower 160 mg/m² level. Disease stabilization persisted even after therapy discontinuation in some cases, a result that suggests faridoxorubicin’s potential to generate durable tumor control without cumulative toxic exposure. Avacta Therapeutics noted that many soft tissue sarcomas express fibroblast activation protein directly on tumor cells, unlike epithelial malignancies where expression is confined to cancer-associated fibroblasts. This direct tumor cell targeting may enhance local drug activation and explain the observed activity even at submaximal doses.

How does faridoxorubicin’s cardiac safety profile compare with doxorubicin and liposomal analogs?

One of the most compelling elements of Avacta Therapeutics’ Phase 1a data is the clean cardiac safety profile observed, despite faridoxorubicin being dosed at levels significantly higher than what would be tolerable with traditional anthracyclines. Echocardiographic assessments revealed no Grade 3 or higher cardiac adverse events at any dose level, including those patients treated up to a cumulative equivalent of 550 mg/m² of conventional doxorubicin.

Only two patients in the trial showed echocardiogram changes consistent with mild adverse effects. One patient treated at 120 mg/m² experienced Grade 2 cardiac failure and was previously documented as a dose-limiting toxicity case. Another patient exhibited minor changes at 500 mg/m². Importantly, none of the patients treated at the maximum cumulative level displayed any signs of cardiac toxicity. These results present a stark contrast to the safety warnings on conventional and liposomal doxorubicin labels, both of which highlight increased cardiac risk beyond the 450 mg/m² threshold.

This absence of cardiotoxicity, even at high doses, supports the core thesis behind the pre|CISION platform: that chemotherapies can be delivered at therapeutic doses with limited off-target exposure. Analysts believe this could significantly extend the use of doxorubicin analogs in solid tumor indications where cumulative toxicity has historically capped long-term efficacy.

What do pharmacokinetic and biopsy data reveal about pre|CISION’s tumor-targeting performance?

Supporting the observed safety outcomes, pharmacokinetic and biopsy analyses demonstrated that plasma and normal tissue exposure to active doxorubicin remained low even at elevated doses of faridoxorubicin. The tumor-to-plasma concentration ratio was found to exceed 100:1, indicating highly selective release within the tumor microenvironment.

Biopsy data collected 24 hours post-dosing confirmed intratumoral cleavage of the prodrug across all tested tumors, including those expressing low levels of FAP (1+ expression). These findings suggest that the pre|CISION platform is capable of achieving efficient cleavage and drug activation even in malignancies with minimal FAP presence, potentially expanding its applicability across a wide range of cancer types.

Moreover, tumor concentrations were shown to be dose-dependent, meaning that increasing the administered dose of faridoxorubicin directly correlates with higher payload concentrations at the tumor site. This is particularly significant for oncology developers seeking to maximize on-target efficacy without scaling systemic exposure.

What is the broader investor outlook and what milestones lie ahead for Avacta Therapeutics?

Avacta Therapeutics is continuing to enroll patients in its Phase 1b expansion cohorts, with more mature data from salivary gland cancer patients anticipated by the end of 2025. If the ongoing trial continues to deliver strong durability and safety, the program could advance into Phase 2 or attract regulatory attention for accelerated development in rare tumor indications.

The pre|CISION platform itself represents a potential new modality within targeted chemotherapy. Unlike antibody-drug conjugates, which rely on surface antigen targeting, Avacta Therapeutics’ platform works within the tumor stroma, offering an avenue for treating malignancies with limited surface marker expression. The success of faridoxorubicin could also validate the broader pipeline, which includes dual payload peptide-drug conjugates currently in preclinical and early clinical development.

Recent institutional participation in the company’s £16 million equity raise further underscores market confidence in the platform’s potential. However, public market reaction remains measured, with shares of Avacta Therapeutics closing flat on October 20, 2025, suggesting that upcoming Phase 1b readouts and regulatory updates may serve as the next major catalysts.

Analysts believe the real test for Avacta Therapeutics will be whether it can translate early safety and pharmacology wins into consistent tumor response and long-term disease control across broader, more diverse cancer populations.

What are the key takeaways from Avacta Therapeutics’ Phase 1a data on faridoxorubicin?

Faridoxorubicin, developed using Avacta Therapeutics’ tumor-activated pre|CISION® platform, continues to show strong clinical potential in Phase 1a trials across multiple solid tumors. Below is a summary of the most significant findings and their implications:

• Median progression-free survival has not been reached in salivary gland cancer patients, with follow-up suggesting over twice the duration compared to benchmark cohorts.

• A 91 percent disease control rate was observed in patients receiving 250 mg/m² or higher, indicating robust anti-tumor activity without the need for dose reductions.

• No maximum tolerated dose was identified in the trial despite escalating doses up to 385 mg/m²—about four times higher than standard doxorubicin regimens.

• Cardiac safety profile remains clean across all dosing levels, with no Grade 3 or higher cardiac adverse events even at cumulative exposure equivalent to 550 mg/m².

• Biopsy and pharmacokinetic data confirm tumor-selective drug release and minimal systemic exposure, with tumor-to-plasma doxorubicin concentration ratios exceeding 100:1.

• Pre|CISION demonstrated activation even in tumors with low FAP expression, validating its broader applicability beyond fibroblast-rich malignancies.

• Early signs of durable disease stabilization were observed in soft tissue sarcoma patients, including responses at low-dose levels.

• The next milestone includes Phase 1b expansion data from salivary gland cancer cohorts expected by year-end 2025, which may guide further development strategy.