AVA6000 Elicits Clinically Meaningful Tumor Shrinkage in Salivary Gland Cancer

Treatment with the investigative AVA6000 peptide drug conjugate consisting of doxorubicin (Adriamycin) led to clinically meaningful tumor shrinkage in patients with fibroblast activation protein-alpha (FAP)–positive salivary gland cancer, a disease without a defined standard treatment in the metastatic setting.1

Data from a phase 1a trial (NCT04969835) showed that 5 of 10 patients had tumor shrinkage after receiving a 250 mg/m2 dose of AVA6000 or greater, with 1 confirmed partial response (PR; 45% tumor shrinkage) and 4 minor responses (MR; 10% to 19.5% tumor shrinkage), per RECIST 1.1 criteria. The 1 confirmed PR was observed at 12 weeks with an ongoing response, although the patient has discontinued treatment with AVA6000 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, although they had low to mid-level FAP expression in cancer-associated fibroblasts alone.

Among these 10 patients, 6 are continuing treatment. An additional 2 reached the maximum treatment cycles and are in follow-up for progression-free survival (PFS). The agent’s safety profile demonstrated a reduction in severe hematologic and cardiac toxicities associated with the conventional dose of doxorubicin at 75 mg/m2 every 3 weeks. Disease progression was reported in 1 patient, resulting in a disease control rate of 90% in the salivary gland cancer cohort.

“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,” Christina Coughlin, MD, PhD, chief executive officer of Avacta Therapeutics, stated in the news release. “Salivary gland cancer is a devastating disease with no established standard of care treatment options. AVA6000 demonstrated clinically meaningful tumor shrinkage in [patients with] salivary gland cancer, highlighting its potential as an important new treatment option for patients with salivary gland cancer and other solid tumors.”

The favorable efficacy and safety data shown in this phase 1a trial supported the initiation of 3 expansion cohorts for the phase 1b portion of the trial. These cohorts include patients with triple-negative breast cancer, soft tissue sarcoma, and salivary gland cancer, who will be treated with AVA6000 in the first- and second-line setting.

In the dose-escalation stage of the phase 1a trial, AVA6000 is administered once every 3 weeks in arm 1 and once every 2 weeks in arm 2. A maximum tolerated dose has not yet been established in either arm.

Patients eligible for the trial are at least 18 years of age.2 The phase 1a portion enrolled patients with tumors reported to be FAP-positive with histologically or cytologically confirmed locally advanced (unresectable) and/or metastatic salivary gland, urothelial, ovarian, or breast cancers that have relapsed or progressed on standard of care or are intolerable to standard of care; those with soft tissue sarcoma who are treatment naive in the locally advanced (unresectable) or metastatic setting and anthracycline naive in any setting, and would be a candidate for doxorubicin treatment; or patients who have 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 have discontinued treatment due to doxorubicin-related intolerance or toxicity.

“We look forward to continuing to work with our investigators and the broader community to explore [the] potential [of AVA6000] in salivary gland cancer and other cancers,” Coughlin concluded in the news release.1 “We are thrilled to begin enrollment in the expansion cohorts, and this part of the trial will also be conducted in less heavily pretreated patients which will allow us to better understand the potential of AVA6000 in these disease settings with high unmet need.”

References

1. Avacta announces positive new data from the AVA6000 phase 1 trial demonstrating clinically meaningful tumor shrinkage in patients with salivary gland cancers. New Release. Avacta Therapeutics. January 16, 2025. Accessed January 17, 2025. https://avacta.com/avacta-announces-positive-new-data-from-the-ava6000-phase-1-trial-demonstrating-clinically-meaningful-tumor-shrinkage-in-patients-with-salivary-gland-cancers/
2. A study evaluating the safety, pharmacokinetics and early efficacy of AVA6000 in solid tumors. ClinicalTrials.gov. Updated December 18, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT04969835