NADOM trial: Neoadjuvant/adjuvant trial of darovasertib in ocular melanoma (OM).

person Roderick O'day Royal Victorian Eye and Ear Hospital, Melbourne, Australia info_outline Roderick O'day, Max Conway, Li-Anne Lim, John McKenzie, Victoria Atkinson, William Glasson, Lindsay McGrath, Svetlana Cherepanoff, Elin Gray, Matthew A. Maurer, Michael O'Quigley, Mark J. Shackleton, Anthony M. Joshua

Authors person Roderick O'day Royal Victorian Eye and Ear Hospital, Melbourne, Australia info_outline Roderick O'day, Max Conway, Li-Anne Lim, John McKenzie, Victoria Atkinson, William Glasson, Lindsay McGrath, Svetlana Cherepanoff, Elin Gray, Matthew A. Maurer, Michael O'Quigley, Mark J. Shackleton, Anthony M. Joshua Organizations Royal Victorian Eye and Ear Hospital, Melbourne, Australia, University of Syndey, Sydney, Australia, Princess Alexandra Hospital, Greenslopes Private Hospital and University of Queensland, Brisbane, Australia, Queensland Institute of Medical Research Berghofer, Herston, Australia, Terrace Eye Centre, Brisbane, Australia, St Vincent's Pathology, Darlinghurst, Australia, Edith Cowan University, Joondalup, Australia, IDEAYA Biosciences, South San Francisco, CA, Ideaya Biosciences, South San Francisco, CA, Department of Oncology, Alfred Health and Monash University, Melbourne, Australia, Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, NSW, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Ideaya Biosciences Background: Darovasertib (Daro) is a novel inhibitor of PKC, that has pre-clinical activity in GNAQ/GNA11 tumours including ocular melanoma. A recently completed clinical trial of Daro monotherapy in metastatic OM with a response rate of 11%, and DCR of 78% with only mild manageable toxicity, suggesting utility in localized disease and in the adjuvant setting. Methods: NADOM is an investigator-initiated window-of-opportunity phase 2 clinical trial open in 3 centers across Australia. Eligible patients include patients planned for enucleation, ECOG 0-1 with adequate organ function. The primary objective is the feasibility and safety of neoadjuvant Daro in a pilot cohort of 12 patients. Secondary objectives include the effect of Daro on circulating biomarkers (including CTCs and ctDNA), imaging assessments (MRI, FDG-PET and ocular ultrasound), pharmacokinetic and pharmacodynamic correlates and radiographic PFS in the adjuvant setting. Treatment comprises a neo-adjuvant period of treatment of up to 6 months at ophthalmologist discretion with Daro (300mg bid) before definitive management. Patients who demonstrated radiological, biomarker or clinical response are then offered an adjuvant period of treatment for up to 6 months following integrated consensus at multi-disciplinary ocular oncology meetings. DSMB meetings are scheduled to ensure clinical and peri-operative safety regularly. Enrolment commenced in November 2022 and accrual is ongoing in the 6 month neo-adjuvant cohort. Results: To date, an initial safety cohort of 1 month of neo-adjuvant treatment has been cleared following DSMB review. Conclusions: Recruitment is ongoing and expected to complete in late 2023. Clinical trial information: NCT05187884.