Type of Participant and Disease Characteristics 1. Has histologically or cytologically confirmed melanoma. 2. Has unresectable Stage III or Stage IV melanoma, per AJCC 8th Edition Staging Criteria (see Appendix 9), not amenable to local therapy. 3. Has the presence of at least 1 measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR. a. Cutaneous lesions and other superficial lesions are not considered measurable lesions but may be considered as nontarget lesions. b. If participants have only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from the nontarget lesion or archival tissue. If biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained post-biopsy and measurable disease confirmed by BICR. c. Lesions that are in an area that has been previously irradiated should not be considered measurable unless there has been documented growth of the lesions since the completion of radiation. 4. Has been untreated for advanced disease except as follows: a. BRAF V600 mutation-positive melanoma may have received SOC targeted therapy as 1L therapy for advanced disease (eg, BRAF/MEK inhibitor, alone or in combination). Note: Prior 1L therapy for advanced disease with targeted therapy is permitted if it was completed at least 4 weeks before randomization, disease progression has been documented radiologically and all related AEs have either returned to baseline or stabilized (resolution of toxic effect(s) to Grade 1 or less [except alopecia and Grade 2 neuropathy]). b. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-PD-1 therapy, anti-CTLA-4 or Interferon) is permitted. Prior anti-PD-1 therapy will only be permitted if relapse did not occur during treatment or within 6 months of treatment discontinuation. No other prior adjuvant or neoadjuvant therapy will be allowed. Note: Both prior adjuvant or neoadjuvant and 1L therapy for advanced disease with targeted therapy (eg, BRAF/MEK inhibitor, alone or in combination) is not allowed. 5. Has documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during Screening (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible). 6. Has provided a tumor biopsy. a. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized/allocated. b. Tumor sample should be freshly obtained (strongly preferred). In cases where newly obtained tissue is not possible to provide, an archival sample may be acceptable after discussion with the Sponsor. c. If a fresh tissue sample is submitted, it is preferred that the tumor biopsy is not obtained from a lone target lesion. If the biopsy specimen was obtained from a lone target lesion, a repeat screening CT must be obtained post-biopsy and measurable disease confirmed by BICR. Demographics 7. Is male or female from 18 years to 120 years at the time of signing the informed consent. 8. Has an ECOG performance status 0 to 1 (as assessed within 7 days of the first dose of study intervention, see Appendix 10). Male Participants Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days, corresponding to time needed to eliminate study intervention(s) after the last dose of study intervention: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below: " Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. " Male participants must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex. Female Participants Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: ·ð Is not a WOCBP OR ·ð Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days, corresponding to the time needed to eliminate any study intervention(s) after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. ·ð A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Informed Consent 11. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. Additional Categories 12. Have adequate organ function as detailed in Table 1. Specimens must be collected within 7 days prior to the first dose of study intervention. 13. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy). If the participant received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity (resolved to d" Grade 1) and/or complications from the intervention. Note: Grade 2 hypothyroidism will be allowed.

Medical Conditions 1. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, topical steroids, or local steroid injections would not be excluded from the study. 2. Has a known additional malignancy that is progressing or requires active treatment within the past 2 years. Exceptions to the secondary malignancy exclusion include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, new nonulcerated primary melanoma <1 mm in depth with no nodal involvement, Grade 1 follicular lymphoma or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy. 3. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided they are stable (without evidence of progression by imaging prior to the first dose of study intervention as evidenced by 2 scans at least 4 weeks apart providing stability, and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases confirmed by repeat imaging, and have not required steroids for at least 14 days before study intervention. The second scan showing stability may be used as baseline scan if acquired within the Screening Phase. Note: Participants with asymptomatic previously untreated brain metastases may participate provided there are d"3 total lesions in the brain and their longest diameter is <1 cm. Stability of these lesions does not need to be confirmed by repeat imaging. Baseline MRI brain scan will be obtained for all participants. Brain CT scan should only be used when MRI is contraindicated. The second brain MRI showing stability may be used as baseline scan if acquired within the Screening Phase. 4. Has ocular or mucosal melanoma. 5. Has known hypersensitivity to active substances or any of their excipients. For a list of excipients, refer to the respective IB. 6. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 7. Has an active infection requiring systemic therapy. 8. Has known history of human immunodeficiency virus (HIV, HIV 1/2 antibodies). No testing of HIV is required unless mandated by local health authority (see Appendix 11 for country-specific requirements). 9. Has known history of hepatitis B (defined as HBsAg reactive) or known hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority (see Appendix 11 for country-specific requirements). 10. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis. 11. Has a history of active tuberculosis (TB, Bacillus tuberculosis). (See Appendix 11 for country-specific requirements). 12. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: In the event that more than 72 hours have elapsed between the Screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative in order for the participant to start receiving study intervention. Prior/Concomitant Therapy 13. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, TIGIT). Note: Please see exceptions (Inclusion Criterion 4b). 14. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to d"Grade 1 or baseline. Participants with d"Grade 2 neuropathy and/or d"Grade 2 endocrinopathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study intervention. 15. Has received prior radiotherapy within 2 weeks of the first dose of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. 16. Has had major surgery (<3 weeks prior to first dose of study intervention). Note: If the participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of study intervention. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. 17. Has received a live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Prior/Concurrent Clinical Study Experience 18. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the Follow-up phase of an investigational study may participate if it has been 4 weeks since the last dose of the previous investigational agent. Diagnostic Assessments None. Other Exclusions 19. Has a history or has current evidence of any condition, therapy, or laboratory abnormality that might confound the results of this substudy, interfere with the participation for the full duration of this substudy, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of this substudy, starting with the Screening visit through 120 days after the last dose of study intervention. 21. Has had an allogeneic tissue/solid organ transplant.