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

Abstract

TPS9612 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 .