Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)

Inclusion Criteria:

• HLA-A*02:01-positive

• unresectable Stage III or Stage IV non-ocular melanoma

• archival tumor tissue sample or a newly obtained biopsy of a tumor lesion notpreviously irradiated has been provided.

• measurable or non-measurable disease per RECIST 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

• If applicable, must agree to use highly effective contraception

• Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the Informed Consent (ICF) and protocol

• Must agree to provide protocol specified samples for biomarker analyses.

Exclusion Criteria:

• Pregnant or lactating women

• diagnosis of ocular or metastatic uveal melanoma

• history of a malignant disease other than those being treated in this study

• ineligible to be retreated with pembrolizumab due to a treatment-related AE

• known untreated or symptomatic central nervous system (CNS) metastases and/orcarcinomatous meningitis

• previous severe hypersensitivity reaction to treatment with another monoclonalantibody (mAb)

• active autoimmune disease requiring immunosuppressive treatment

• clinically significant cardiac or pulmonary disease or impaired cardiac function

• known psychiatric or substance abuse disorders

• received prior treatment with a licensed or investigative Immune-mobilizingmonoclonal T-cell receptor Against Cancer (ImmTAC) medication or who have notcompleted adequate washout from prior medications.

• received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb,ipilimumab, and BRAF TKI regimen) within 14 days of first dose

• received cellular therapies within 90 days of study intervention

• ongoing Common Terminology Criteria for Adverse Events(CTCAE) Grade ≥ 2 clinicallysignificant who in the opinion of the investigator could affect the outcome of thestudy

• received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of first dose

• have not progressed on treatment with an anti-PD(L)1 mAb

• have not received prior treatment with an approved anti-CTLA-4 mAb

• a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen

• currently participating or have participated in a study of an investigational agentor using an investigational device within 30 days of the first dose

• known history of chronic viral infections such as hepatitis B virus (HBV) orhepatitis C virus (HCV)

• known clinically significant pulmonary or cardiac disease or impaired lung orcardiac function

• Out of range Laboratory values

• history of allogenic tissue/solid organ transplant