Salivary Gland Cancer | Image Credit:
© shahzaib – stock.adobe.com
Treatment with the first-generation pre|CISION peptide drug conjugate AVA6000 led to early efficacy and safety signals in patients with previously treated, locally advanced or metastatic salivary gland cancers, according to data from the dose-escalation portion of a phase 1 trial (NCT04969835).1
Findings announced by Avacta Therapeutics showed that among patients treated with AVA6000 at a dose of at least 250 mg/m2 (n = 11), 1 achieved a confirmed partial response (PR), defined as a tumor reduction of more than –30% per RECIST 1.1 criteria. Four patients experienced minor responses with tumor reductions between –10% and –19%. The disease control rate (DCR) was 91% with 1 patient experiencing progressive disease.
At a median follow-up of approximately 5 months, the median progression-free survival (PFS) was not reached. Five patients remained on study treatment at data cutoff, and 9 of 11 patients remained free of disease progression.
AVA6000, which features a doxorubicin payload, generated a favorable safety profile compared with conventional doxorubicin. Notably, no instances of severe cardiac toxicity were reported.
“We are very excited to move the development of AVA6000 to the next level to generate data that demonstrates clinically meaningful efficacy and durability of response in patients with previously treated salivary gland cancers,” Alan Ho, MD PhD, chief of the Head and Neck Oncology Service at Memorial Sloan Kettering Cancer Center and a member of the Avacta Scientific Advisory Board, stated in a news release. “It is important to note the high degree of unmet need in this disease where few agents have shown efficacy. I am happy to participate in the trials of AVA6000 in this disease setting in the future.”
During the now-completed dose-escalation portion of the first-in-human phase 1 study, investigators enrolled patients at least 18 years of age with histologically or cytologically confirmed, locally advanced unresectable or metastatic solid tumors likely to be FAP positive, including salivary gland, urothelial, ovarian, or breast carcinoma. Patients were required to have disease relapse or progression following standard-of-care (SOC) therapy or intolerance to SOC treatment.
This portion of the study also included patients with soft-tissue sarcoma who were previously untreated in the advanced setting, naive to anthracycline in any setting, and candidates for doxorubicin; or who received a total doxorubicin dose of less than 150mg/m2 and discontinued treatment due to intolerance or toxicity related to the agent.
The ongoing dose-expansion portion of the study is further evaluating AVA6000 monotherapy in patients with locally advanced or metastatic salivary gland cancers of any histologic subtype who received up to 1 prior line of therapy in the advanced setting; locally advanced or metastatic triple-negative breast cancer who previously received up to 2 prior lines of therapy in the metastatic or advanced setting; and undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma who received up to 1 prior line of therapy in the advanced setting.1 Approximately 20 to 30 patients will be enrolled in each cohort, and multiple patients have been treated in this portion of the trial to date.
In dose expansion, patients in all 3 cohorts are also required to have measurable disease per RECIST 1.1 criteria, and prior anthracycline-based therapy is not allowed.2
The dose-escalation portion of the study examined escalating doses of AVA6000 given once every 3 weeks or once every 2 weeks. The dose-expansion portion is further exploring the recommended dose determined in phase 1a.
Dose-limiting toxicities, safety, and cardiac toxicity are the trial’s primary end points. Pharmacokinetics, ORR, duration of response, PFS, and overall survival are secondary end points.
Full data from the dose-escalation part of the trial will be presented in the second half of 2025 following a further data update expected in the second quarter. Initial data from dose expansion are anticipated at the end of the year.
“We are very pleased to advance to the expansion cohorts in the AVA6000 trial in these three indications with high unmet need,” Christina Coughlin, chief executive officer of Avacta Therapeutics, stated in a news release. “Our development of AVA6000 is proceeding according to plans and today’s new data demonstrate the durability of the responses we have observed in the salivary gland cancers indication. We believe that AVA6000 has an important role to play in the clinic, given our preliminary efficacy data and the large commercial market size of conventional doxorubicin”
### **References**
1. Avacta announces promising early efficacy and safety data for AVA6000 in the phase 1a dose escalation and ongoing enrollment in the phase 1b expansion cohorts. News release. Avacta Therapeutics. March 7, 2025. Accessed March 13, 2025. https://avacta.com/avacta-announces-promising-early-efficacy-and-safety-data-for-ava6000-in-the-phase-1a-dose-escalation-and-ongoing-enrollment-in-the-phase-1b-expansion-cohorts/
2. A study evaluating the safety, pharmacokinetics and early efficacy of AVA6000 in solid tumours. ClinicalTrials.gov. Updated December 18, 2024. Accessed March 13, 2025. https://clinicaltrials.gov/study/NCT04969835