Avacta Updates Phase 1 Data of AVA6000 at ESMO Congress, Showing Ongoing Durable Responses in Solid Tumors

Avacta Group plc has presented promising updated data from its Phase 1a clinical trial of AVA6000 at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. AVA6000, a pioneering peptide drug conjugate (PDC), involves doxorubicin linked with a peptide moiety that is specifically activated by Fibroblast Activation Protein (FAP) in the tumor microenvironment. The trial, aimed at patients with FAP-positive solid tumors, has shown that AVA6000 is well-tolerated with early signs of efficacy, particularly in FAP-high diseases.

The trial tested two dosing regimens: every three weeks (Q3W) and every two weeks (Q2W). Both schedules showed AVA6000 to be safe, with a favorable cardiac safety profile and reduced toxicities compared to conventional doxorubicin. Specifically, there were fewer instances of severe neutropenia and no cases of febrile neutropenia in the AVA6000 trial compared to conventional doxorubicin trials. Additionally, AVA6000 exhibited fewer cardiac side effects and reduced issues that impact patient quality of life, such as nausea and mouth sores.

A total of 57 patients participated in the study, with 49 being evaluable for efficacy. Tumor responses were categorized based on FAP expression levels, focusing on FAP-high and FAP-mid cancers. Notable efficacy results include three partial responses and four minor responses among patients with FAP-high cancers. Particularly, a 79-year-old male with salivary gland cancer achieved a durable partial response lasting over 18 weeks. Another partial response was observed in a patient with dedifferentiated liposarcoma who previously failed two lines of therapy.

Pharmacokinetically, AVA6000 shows significant changes compared to conventional doxorubicin. The plasma half-life of released doxorubicin was extended by about 40%, and there were reductions in peak plasma concentration and peripheral distribution volume. This suggests a more focused delivery of doxorubicin to tumor tissues, sparing normal tissues from high drug exposure.

Biopsies from the trial revealed that even lower levels of FAP activity were sufficient to release the drug within the tumor environment, a finding that supports the potential of AVA6000 to treat a broad range of solid tumors with varying levels of FAP expression.

Avacta's pre|CISION™ technology, which underpins AVA6000, aims to activate therapeutic agents specifically within the tumor microenvironment, thereby minimizing systemic toxicity and improving patient outcomes. This approach leverages the elevated FAP levels in many solid tumors to locally release the active drug from its inert form, sparing healthy tissues and enhancing tolerability.

The positive data from this trial provides robust clinical validation for AVA6000 and suggests that the pre|CISION™ platform could significantly impact cancer treatment by enabling the targeted delivery of potent therapeutics. By focusing on the tumor-specific enzyme FAP to protect normal tissues from toxic drugs, Avacta aims to improve therapeutic outcomes with fewer side effects.

Avacta's CEO, Christina Coughlin, expressed optimism about the potential of the pre|CISION™ platform to revolutionize cancer treatment. With nearly six months of additional follow-up data, the company is excited to advance to the next stage of development, leveraging the findings from this trial to enhance its innovative cancer treatment pipeline.

In summary, the Phase 1a trial of AVA6000 has demonstrated the drug's safety, tolerability, and preliminary efficacy in patients with FAP-positive solid tumors. The results support the continued development of AVA6000 and the exploration of the pre|CISION™ platform's broader applicability in oncology.