A RANDOMIZED, PHASE 3, OPEN-LABEL STUDY OF NEOADJUVANT DAROVASERTIB IN SUBJECTS WITH PRIMARY NON-METASTATIC UVEAL MELANOMA (OptimUM-10)

Trial status: Authorised Both Cohorts: ORR_UM, defined as the rate of best overall response (complete response [CR] or partial response [PR]) Response defined as: o CR: Complete regression of tumor by ultrasound (US) and fundus photography (FP); o PR: Decrease in product of diameters by US and/or FP by ≥ 20% or decrease in thickness by US by ≥ 20% from baseline;, Both Cohorts: EFS, defined as the time from randomization to the first documented date of treatment failure (including disease progression, local/distant recurrence, or death, whichever occurs first), Both Cohorts: Incidence of all treatment-emergent AEs (TEAEs), serious adverse events (SAEs) and clinically significant laboratory test abnormalities, and changes to electrocardiograms (ECGs) and vital signs, Both Cohorts: • ORR_UM • DCR, defined as the proportion of CR, PR, or SD, Both Cohorts: Proportion of subjects with improvement in ETDRS BCVA letters and/or Snellen lines, Cohort 1: Proportion of subjects with clinically significant ME (%ME defined optical coherence tomography [OCT] finding, vision loss, and initiation of vascular endothelial growth factor inhibitor [VEGFi] administration) measured from the time of randomization and completion of PB, Cohort 1: Proportion of subjects with 20/200 vision or worse (%20/200) from the time of randomization and completion of PB, Cohort 1: Proportion of subjects with significant reduction of radiation dose (defined as a ≥ 20% reduction) delivered to key eye structures including, but not limited to, the macula, optic disc/nerve, and lens, Cohort 1:Proportion of subjects with ME on OCT from the time of completion of PB ME by OCT defined as the presence of intraretinal fluid (cystoid edema) on OCT, Cohort 1:Proportion of subjects with radiationrelated ocular toxicities at 6, 12, 18, 24, 30, and 36 months post PB • The incidence and severity of radiation induced ocular toxicities Cohort 1: Proportion of moderate to high risk of visual impairment (MHRVI) subjects with loss of Best Corrected Visual Acuity (BCVA) of ≥ 15 letters using Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA (%VL15) measured from the time of randomization and completion of PB, Cohort 2: Eye preservation rate

Both Cohorts: ORR_UM, defined as the rate of best overall response (complete response [CR] or partial response [PR]) Response defined as: o CR: Complete regression of tumor by ultrasound (US) and fundus photography (FP); o PR: Decrease in product of diameters by US and/or FP by ≥ 20% or decrease in thickness by US by ≥ 20% from baseline;, Both Cohorts: EFS, defined as the time from randomization to the first documented date of treatment failure (including disease progression, local/distant recurrence, or death, whichever occurs first), Both Cohorts: Incidence of all treatment-emergent AEs (TEAEs), serious adverse events (SAEs) and clinically significant laboratory test abnormalities, and changes to electrocardiograms (ECGs) and vital signs, Both Cohorts: • ORR_UM • DCR, defined as the proportion of CR, PR, or SD, Both Cohorts: Proportion of subjects with improvement in ETDRS BCVA letters and/or Snellen lines, Cohort 1: Proportion of subjects with clinically significant ME (%ME defined optical coherence tomography [OCT] finding, vision loss, and initiation of vascular endothelial growth factor inhibitor [VEGFi] administration) measured from the time of randomization and completion of PB, Cohort 1: Proportion of subjects with 20/200 vision or worse (%20/200) from the time of randomization and completion of PB, Cohort 1: Proportion of subjects with significant reduction of radiation dose (defined as a ≥ 20% reduction) delivered to key eye structures including, but not limited to, the macula, optic disc/nerve, and lens, Cohort 1:Proportion of subjects with ME on OCT from the time of completion of PB ME by OCT defined as the presence of intraretinal fluid (cystoid edema) on OCT, Cohort 1:Proportion of subjects with radiationrelated ocular toxicities at 6, 12, 18, 24, 30, and 36 months post PB • The incidence and severity of radiation induced ocular toxicities

Age group: 65+ years, 18-64 years Gender: Female, Male Target enrollment: 297 participants