NADOM: This phase II study is evaluating how effective targeted therapy (darovasertib) is people with occular (uveal) melanoma who are planned to undergo surgeryNeoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma

Exclusion

• Previous treatment with a PKC inhibitor
• Have AEs from prior anti-cancer therapy that have not resolved to Grade =1 except for alopecia, prior peripheral neuropathy, or anaemia. Endocrinopathies resulting from previous immunotherapy are considered part of the medical history and not an AE.
• Untreated or symptomatic malignant lesions in the central nervous system (CNS).
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related illness.
• Active infection requiring therapy (except nail fungus), positive tests for Hepatitis B surface antigen (HBsAg) with detected Hepatitis B virus (HBV) DNA or positive Hepatitis C antibody with detected Hepatitis C virus (HCV) RNA.
• Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder or defect e.g., malabsorption disorder such as Crohn's disease or ulcerative colitis, that would interfere with absorption of Darovasertib.

• Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following (see Appendix 4):

  • known to be strong inducers or inhibitors of CYP3A4/5
  • known to be substrates of CYP3A4/5, OAT3, OATP1B1, and MATE1/2-Kwith a narrow therapeutic index

• Females who are pregnant or breastfeeding:

  • Women of childbearing potential must not be considering getting pregnant during the study.
  • Patients of reproductive potential (male & female) must practice an effective method of contraception during treatment and for 30 days following the last dose of Darovasertib. Patients unwilling to do so will be excluded.

• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

  • History or presence of ventricular tachyarrhythmia
  • Presence of unstable atrial fibrillation (ventricular response > 100 BPM); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria
  • Angina pectoris or acute myocardial infarction = 6 months prior to starting study drug
  • Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
  • Patients with a drug eluting stent for cardiovascular purposes placed = 6 months prior to starting study drug
  • Corrected QT interval using Fridericia's method (QTcF) > 480 msec on baseline ECG (mean of baseline values). If electrolytes are abnormal, they may be corrected, and baseline ECGs should be repeated (Appendix 5).
• Known to have previously received Darovasertib
• Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.