Avacta Therapeutics has announced positive outcomes from its Phase Ia trial of AVA6000, an investigational drug for solid tumors, with a focus on salivary gland cancer (SGC). The trial results indicate clinically meaningful tumor shrinkage in patients with fibroblast activation protein-positive (FAP-positive) SGC, a disease lacking a standard treatment approach in the metastatic setting.
Clinical Efficacy in Salivary Gland Cancer
In the Phase Ia trial (NCT04969835), ten subjects received a dose of 250mg/m² or higher of AVA6000. Five of these patients experienced tumor shrinkage, including one confirmed partial response (PR) with a 45% tumor shrinkage and four minor responses (MR) ranging from 10% to 19.5% tumor shrinkage, according to RECIST 1.1 criteria. The confirmed PR was observed at 12 weeks, with an ongoing response, although the patient discontinued treatment after reaching their lifetime maximum of doxorubicin exposure. One patient who achieved a MR experienced rapid and complete regression of large skin and visceral metastasis, despite low to mid-level FAP expression in cancer-associated fibroblasts alone.
Tolerability and Safety Profile
AVA6000's tolerability has been confirmed across both dosing schedules, demonstrating a significant reduction in toxicities, and no maximum tolerated dose has been identified. The agent's safety profile showed a reduction in severe hematologic and cardiac toxicities typically associated with conventional doses of doxorubicin at 75 mg/m2 every 3 weeks. Disease progression was reported in one patient, resulting in a disease control rate of 90% in the salivary gland cancer cohort.
Expansion Cohorts and Future Development
Encouraged by the favorable safety and efficacy data, Avacta has initiated three Phase Ib expansion cohorts to further explore the therapy in soft tissue sarcoma, SGC, and triple-negative breast cancer. Subject screening for these cohorts is ongoing, with the first US patients expected to begin treatment soon. These cohorts will be treated with AVA6000 in the first- and second-line settings, allowing for a better understanding of its potential in these disease settings with high unmet need.
Mechanism of Action and Target Population
AVA6000 is designed to target FAP-positive solid tumors. The Phase Ia trial enrolled patients with locally advanced and/or metastatic solid tumors known to be FAP-positive, including those with salivary gland, urothelial, ovarian, or breast cancers that have relapsed or progressed on standard of care, or are intolerant to standard of care. The trial also included patients with soft tissue sarcoma who are treatment-naive in the locally advanced or metastatic setting and anthracycline-naive in any setting, and would be a candidate for doxorubicin treatment. Patients who had been treated with a total doxorubicin dose of less than 150 mg/m2 in any setting at less than 2 cycles of 75 mg/m2 every 3 weeks and had discontinued treatment due to doxorubicin-related intolerance or toxicity were also eligible.
Management Quotes
Avacta Therapeutics CEO Christina Coughlin, MD, PhD, stated, "These data highlight the transformative potential of our precision peptide drug conjugates in expanding the efficacy of highly potent therapeutics and support our growing optimism in this program. We are thrilled to begin enrollment in the expansion cohorts, and this part of the trial will also be conducted in less heavily pre-treated patients, which will allow us to better understand the potential of AVA6000 in these disease settings with high unmet need."
