Interim data show preliminary safety, efficacy of AU-011 for choroidal melanoma
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The majority of patients with choroidal melanoma treated with AU-011 have maintained vision and experienced tumor control and reduced growth rate, according to interim results of a phase 1b/2 open-label clinical trial.
“Preliminary results show that AU-011 for choroidal melanoma is both safe and effective. One and two cycles of AU-011 were well tolerated. Inflammation is noted and has been manageable, and steroid therapy can be effective to control inflammation once it begins,” Prithvi Mruthyunjaya, MD, MHS, said at the virtual Association for Research in Vision and Ophthalmology meeting.
Fifty-six subjects have been treated in the ongoing trial. Researchers have evaluated the safety and efficacy of AU-011 (Aura Biosciences), a novel targeted investigational therapy, for the treatment of choroidal melanoma. Participants with a clinical diagnosis of choroidal melanoma with tumor thickness of 1.2 mm to 3.4 mm and largest basal diameter of 16 mm or less were included. The participants received intravitreal administration of AU-011 at doses of 20 µg, 40 µg or 80 µg followed by light activation from a 689 nm laser at a fluence of 50 J/cm2, Mruthyunjaya said.
Eight escalation cohorts underwent regimens consisting of one, two or three weekly treatments with AU-011 followed by one or two laser applications. The researchers have started to enroll for a phase 3 study, with participants receiving two cycles of three weekly treatments with 80 µg and two laser administrations separated by 12 weeks. Twenty-one participants with documented tumor growth 0.3 mm or greater within 2 years, a thickness between 0.5 mm to 3 mm, largest basal dimension of 13 mm or less, and tumor volume of 50 mm3 are eligible for the phase 3 study, he said.
In the phase 1b/2 trial, the majority of treated patients had anterior chamber or vitreous inflammation, and 41.1% experienced an increase in IOP. These patients were managed with steroids and topical ocular antihypertensives, and the majority resolved without clinical sequelae, Mruthyunjaya said.
Vision efficacy findings were favorable for visual acuity preservation. Vision failure was defined as a long-term decrease in vision of more than 15 letters or three lines. Overall, vision preservation rate for all participants was 93%. In phase 3 eligible participants, the vision preservation rate was 95%. For 15 participants who received the therapeutic regimen proposed for the phase 3 study, the vision preservation rate was 93%, he said.
Overall, tumor control was favorable. Tumor progression was defined as growth in both thickness and largest basal diameter. In the overall cohort, 66% of participants experienced tumor control. In the phase 3 eligible participants, 100% experienced tumor control, he said.
Tumor growth was also controlled after AU-011 treatment. In the phase 3 eligible participants, a projected growth rate of 0.8 mm per year in tumor thickness was calculated based on the individual growth rates of the tumors for those patients. After treatment, phase 3 eligible patients and those receiving the phase 3 treatment regimen experienced a statistically significant reduction in tumor growth rate, Mruthyunjaya said.
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Mruthyunjaya P, et al. A phase 1b/2 open-label clinical trial to evaluate the safety and efficacy of AU-011 for the treatment of choroidal melanoma. Presented at: Association for Research in Vision and Ophthalmology annual meeting; June 12, 2020 (virtual meeting).
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