Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma

Inclusion Criteria: Histologically or cytologically confirmed untreated metastatic uveal melanoma (mUM). HLA-A\*0201 genotype positive as assessed using a CLIA-certified blood typing method and confirmed by central review. * If HLA-A status is not known, blood for HLA-A testing must be submitted during Screening, and HLA-A\*0201 positive status confirmed prior to enrollment using a CLIA- certified blood typing method. * If the patient is known to be HLA-A\*0201 positive, this information must be provided in the Screening packet and centrally reviewed by treating PI and Sponsor-Investigator prior to enrollment. * The following HLA testing methodologies are suitable to determine HLA-A\*0201 positivity: * Multiplex real-time PCR based testing performed by entities including but not limited to Labcorp, and American Red Cross. * HLA testing as part of peripheral blood molecular profiling technology including but not limited to Caris Life Sciences Molecular Profiling Technology. * Patients be willing to undergo ctDNA assessment using Signatera assay. * Have provided newly obtained core biopsy of a tumor lesion not previously irradiated. * Adequate organ function on screening labs obtained within 4 weeks of Week 1 day 1 * Must meet the following criteria related to prior treatment: * No prior systemic therapy in the metastatic or advanced setting including chemotherapy, or targeted therapy. * NOTE: Patients must be tebentafusp naïve. * NOTE: Patients must not have received prior PD-1, CTLA-4, LAG-3 directed Immune Checkpoint Inhibitor therapy delivered in the adjuvant, and/or neoadjuvant settings unless such therapy was received \>6 months prior initial diagnosis of mUM. * No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization. * Prior surgical resection of oligometastatic disease is allowed. * Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in patients with localized disease. * Life expectancy of \>6 months as estimated by the investigator. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening. * Patients have measurable disease according to RECIST v.1.1. * All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug. Exclusion Criteria: * History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies. * Clinically significant cardiac disease or impaired cardiac function, including any of the following: * Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade ≥ 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment. * QTcF \> 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome. * NOTE: If the initial automated QTcF interval is \> 470 msec at screening, for the purpose of determining eligibility, the mean QTcF, based on at least 3 ECGs obtained over a brief time interval (ie, within 30 minutes), should be manually determined by a medically qualified person. * NOTE: Acute myocardial infarction or unstable angina pectoris \< 6 months prior to Screening. * Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to study Day 1. * Presence of active brain metastases. * NOTE: Patients with brain metastases are eligible if all lesions have been treated surgically and/or radiosurgically and there is no evidence of progression for at least 2 weeks by MRI prior to the first dose of study drug. * NOTE: Patients with any evidence of leptomeningeal disease are excluded. * Active infection requiring systemic antibiotic therapy. • NOTE: Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug. * Known history of uncontrolled active human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection. * NOTE: Testing for HIV, HBV and/or HCV is not necessary unless clinically indicated or the patient has a history of HBV/HCV and/or HIV infection. * NOTE: Patients with curatively treated HBV and/or HCV infection may be enrolled. In these instances, HBV (quantitative HBV DNA) and/or HCV (quantitative HCV RNA) resolution must be documented using a quantitative viral load assay. * NOTE: Patients with HIV who are stably controlled on highly active antiretroviral therapy (HAART) therapy with a low HIV viral load may be enrolled. In these instances, stable control is defined as HAART compliant with a CD4 count of ≥200 cells/μL, and low viral load is defined as \<200 copies/mL on tests done during Screening. * Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: * Completely resected carcinoma in situ of any type, resected basal cell and squamous cell carcinomas. * Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; * Any malignancy considered to be indolent that has never required therapy Sponsor-Investigator evaluation. * Any medical condition that would, in the judgment of the Sponsor-Investigator, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results. * Patients receiving systemic steroid therapy or any other immunosuppressive medication at any dose level, as these may interfere with the mechanism of action of study treatment. NOTE: Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable. * History of symptomatic autoimmune disease including: * Interstitial lung disease. * Pneumonitis requiring corticosteroid treatment or current pneumonitis. * Colitis or inflammatory bowel disease. NOTE: However, patients with a history of autoimmune disease who are currently on physiologic hormone repletion (prednisone or equivalent of 10mg or less) and are otherwise asymptomatic may be enrolled. * Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary). * Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass. * Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent. * Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation). * Women of childbearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. * Male patients must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of study drug. * Receipt of live or attenuated vaccinations 2 weeks prior to starting study therapy. Patients may receive vaccinations on treatment.