Adjuvant Tebentafusp in High Risk Ocular Melanoma

Inclusion Criteria:

• Primary non-metastatic UM, except iris melanoma, after definitive treatment eitherby surgery or radiotherapy

• Time from primary treatment smaller than 11 weeks (note that the maximum timebetween primary treatment and randomization is 12 weeks )

• High-risk according to either 1) clinical criteria: TNM (AJCC8) stage III or 2)genetic criteria: monosomy 3 or GEP class 2. Prior to enrolment of the firstpatient, each site will declare which of the two genetic criteria it uses. Patientswith stage I and stage II are only eligible if they meet the genetic criteriondeclared by the site.

• ECOG performance status of 0 or 1

• 18 years or older

• HLA-A*02:01 positivity by local assessment

• No evidence of UM recurrence, as evidenced by the required baseline imagingperformed within 4 weeks prior to randomization

• Adequate organ function

• Time-interval between the end of primary treatment and the randomization less thanor equal to 12 weeks

• Evidence of post-menopausal status or negative urinary or serum pregnancy test forwomen of childbearing potential (WOCBP) within 3 days prior to randomization.

• For patients of childbearing / reproductive potential, agreement to use adequatebirth control measures during the study treatment period and for at least 6 monthsafter the last dose of treatment. A highly effective method of birth control isdefined as a method which results in a low failure rate (i.e., less than 1% peryear) when used consistently and correctly.

• For female subjects who are breast feeding, agreement to discontinue nursing priorto the first dose of study treatment and until 6 months after the last studytreatment.

• Written informed consent according to ICH/GCP and local regulations

Exclusion Criteria:

• Clinically significant cardiac disease or impaired cardiac function, including anyof the following:

• Clinically significant and/or uncontrolled heart disease such as congestive heartfailure (New York Heart Association grade ≥ 2), uncontrolled hypertension, orclinically significant arrhythmia currently requiring medical treatment

• QTcF > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndromebased on at least 3 ECGs obtained over a brief time interval (i.e., within 30minutes)

• Acute myocardial infarction or unstable angina pectoris < 6 months prior toscreening

• Active infection requiring systemic antibiotic therapy. Patients requiring systemicantibiotics for infection must have completed therapy at least 1 week prior torandomization

• Any evidence of severe or uncontrolled systemic disease or active infectionincluding hepatitis B, hepatitis C and known active human immunodeficiency virus (HIV) defined as >200 copies of HIV per ml of blood, active bleeding diatheses orrenal transplant. NOTE: testing for HIV, HBV, and HCV status prior to enrolment isnot necessary unless clinically indicated.

• Participant with history of HBV infection will be eligible if on stable anti-viraltherapy for > 4 weeks prior to the planned first dose of study intervention andviral load confirmed as undetectable during Screening.

• Participant with history of HBC infection will be eligible the participant hasreceived curative treatment and viral load was confirmed as undetectable duringScreening.

• History of another primary malignancy except for adequately treated basal orsquamous cell carcinoma of the skin or cancer of the cervix in situ and with thefollowing exception. Patients with a history of another primary cancer treated withcurative intent more than 3 years before study entry, who are not receiving anyanti-cancer therapy, have a risk of disease recurrence lower than 10% as evaluatedby the local Investigator, and who have no toxicity from previous treatment areeligible.

• Participants with active autoimmune disease requiring immunosuppressive treatment,including inflammatory bowel disease (ulcerative colitis or Crohn's disease), within 2 years of screening. NOTE: The following exceptions are permitted:

• Vitiligo

• Alopecia

• Managed hypothyroidism (on stable replacement doses)

• Asymptomatic adrenal insufficiency (on stable replacement doses)

• Psoriasis

• Resolved childhood asthma/atopy

• Well-controlled asthma

• Type I diabetes mellitus

• Any psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule; thoseconditions should be assessed and discussed with the patient before the enrolment inthe trial.

• Known contraindication to imaging tracer or any product of contrast media and MRIand/or CT contraindications