Azitra, Inc. can now enroll patients in the second cohort of its Phase 1/2 trial for ATR04-484 after the study’s safety review committee cleared the first group. The decision resolves the immediate question of whether the early safety data supports moving forward with the live biotherapeutic designed to treat skin rashes caused by EGFR inhibitors.
The multicenter, randomized, double-blind, vehicle-controlled study (NCT06830863) evaluates the safety and tolerability of topical ATR-04 for adult patients with EGFR inhibitor-associated dermal toxicity. The trial compares ATR04-484 against its vehicle using a 3:1 randomization ratio. Six clinical sites are currently running the study, including MD Anderson Cancer Center and Yale University.
In Cohort 1, seven patients applied 4g of ATR04-484 to their face, chest, and back. This initial dose was followed by a 7-day observation period and then once-daily application for 28 days. The safety review committee based its clearance on data from six of these patients. Cohort 2 is expected to enroll approximately 24 patients who will receive a 4g application once daily for 28 days.
Francisco Salva, Chief Executive Officer of Azitra, called the progression to Cohort 2 an important milestone. He stated that the company believes ATR-04 could be the first live biotherapeutic created specifically for cancer treatment-associated rash. Salva noted that positive safety data from the first cohort supports the company's focus on advancing into the next phase of the trial.
EGFR inhibitors are a significant component of treatment for cancers such as non-small cell lung cancer and colorectal cancer. However, these therapies frequently cause a painful papulopustular skin rash that affects approximately 50% to 80% of patients. The severity of this rash can impair quality of life and often leads to dose reductions, treatment interruptions, or discontinuation of effective cancer therapies.
ATR04-484 is a live biotherapeutic product candidate containing an isolated, naturally derived Staphylococcus epidermidis strain. Researchers selected this strain because preclinical studies showed it could lower levels of IL-36γ and Staphylococcus aureus, two factors that are elevated in patients with this type of rash. To improve safety, engineers modified the strain by deleting an antibiotic resistance gene and introducing auxotrophy to control its growth. Preclinical data indicate that ATR04-484 can reduce levels of IL-36γ, a key pro-inflammatory cytokine, and inhibit the growth of S. aureus.
The U.S. Food and Drug Administration has granted Fast Track designation to ATR04-484 for the treatment of EGFRi-associated rash. This designation recognizes the high unmet medical need for the approximately 150,000 patients affected annually in the United States.