A Phase 1b/2 Open-label Clinical Trial to Evaluate the Safety and Efficacy of AU-011 for the Treatment of Choroidal Melanoma

Learner UI

P. Mruthyunjaya, Ophthalmology, Byers Eye Institute at Stanford University, Palo Alto, California, UNITED STATES|A.C. Schefler, Retina Consultants of Houston, Houston, Texas, UNITED STATES|I.K. Kim, Mass Eye And Ear Infirmary, Boston, Massachusetts, UNITED STATES|C. Bergstrom, Retina Consultants of Carolina, PA, Greenville, South Carolina, UNITED STATES|H. Demirci, Ophthalmology, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, UNITED STATES|T. Tsai, Retina Consultants of Sacramento, Sacramento, California, UNITED STATES|A.R. Bhavsar, Retina Center, Minneapolis, Minnesota, UNITED STATES|A. Capone, Associated Retinal Consultants, PC, Royal Oak, Michigan, UNITED STATES|B. Marr, Ophthalmology, Columbia Univesrsity Medical Center, New York, New York, UNITED STATES|T.A. McCannel, Ophthalmology, UCLA Jules Stein Eye Institute, Los Angeles, California, UNITED STATES|C. Javid, Retina Associates, Tuscon, Arizona, UNITED STATES|P.G. Hovland, Colorado Retina Consultants, Denver, Colorado, UNITED STATES|M.I. Seider, Ophthalmology, Permanente Medical Group, San Francisco, California, UNITED STATES|C. Rich, Aura Biosciences, Boston, Massachusetts, UNITED STATES|C.L. Shields, Wills Eye Hospital, Philadelphia, Pennsylvania, UNITED STATES|

Tag(s) 2020 Annual Meeting, AP: Anatomy and Pathology / Oncology, Scientific presentation

A Phase 1b/2 Open-label Clinical Trial to Evaluate the Safety and Efficacy of AU-011 for the Treatment of Choroidal Melanoma

Description

Purpose:
Choroidal melanoma (CM) is the most common primary ocular malignancy. Most small CMs are treated with radiotherapy which is associated with several adverse effects including vision loss. The safety and efficacy of AU-011, a novel targeted investigational therapy for the treatment of CM, is beingevaluated in an open-label, multi-center, dose escalation and expansion trial.
Methods:
Subjects with a clinical diagnosis of CM with tumor thickness 1.2 - 3.4 mm and largest basal diameter ≤ 16 mm received intravitreal administration of a viral-like particle bioconjugate (AU-011) at doses of 20 µg, 40 µg, or 80µg followed by light-activation with a 689 nm laser at a fluence of 50 J/cm2. Regimens consisting of 1, 2 or 3 weekly treatments with AU-011 each followed by 1 or 2 laser applications have been evaluated in 8 escalation cohorts and 1stexpansion. Enrollment is ongoing in the 2ndexpansion with subjects receiving two cycles of three weekly treatments with 80 µg /2 laser administrations separated by 12 weeks.
Results:
50 subjects have been treated in the trial. Interim results show local tumor control in 33/50 (66%) subjects (23/29 [79%] at therapeutic dose) and maintenance of visual acuity in 46/50 (92%) subjects (27/29 [93%] at therapeutic dose) with up to 24 months follow up. Linear regression was used to estimate tumor growth rates using tumor thickness measurements before and after treatment in subjects with historical documented growth (n=19). Tumor control was seen in 15/19 subjects and the post-treatment growth rate was significantly reduced compared to their historical growth rate (p=0.0056; paired t-test). There has been one treatment-related SAE of severe vision loss. Expected AEs related to treatment including intraocular inflammation and increased IOP were clinically manageable.
Conclusions:
Interim results from this ongoing trial show preliminary safety and efficacy of AU-011. The therapy was well tolerated with maintenance of vision and tumor control in majority of subjects.AU-011 may offer an alternative to radiotherapy for treating small melanomas and high risk indeterminate lesions and further studies are planned to confirm the safety and efficacy.

Prithvi Mruthyunjaya: Commercial Relationship(s);Aura Biosciences:Code C (Consultant);Castle Biosciences:Code C (Consultant) | Amy Schefler: Commercial Relationship(s);Aura Biosciences:Code C (Consultant) | Ivana Kim: Commercial Relationship: Code N (No Commercial Relationship) | Christopher Bergstrom: Commercial Relationship: Code N (No Commercial Relationship) | Hakan Demirci: Commercial Relationship: Code N (No Commercial Relationship) | Tony Tsai: Commercial Relationship: Code N (No Commercial Relationship) | Abdhish Bhavsar: Commercial Relationship: Code N (No Commercial Relationship) | Antonio Capone: Commercial Relationship: Code N (No Commercial Relationship) | Brian Marr: Commercial Relationship(s);Aura Biosciences:Code C (Consultant) | Tara McCannel: Commercial Relationship: Code N (No Commercial Relationship) | Cameron Javid: Commercial Relationship: Code N (No Commercial Relationship) | Peter Hovland: Commercial Relationship: Code N (No Commercial Relationship) | Michael Seider: Commercial Relationship: Code N (No Commercial Relationship) | Cadmus Rich: Commercial Relationship(s);Aura Biosciences:Code E (Employment) | Carol Shields: Commercial Relationship(s);Aura Biosciences:Code C (Consultant)