Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)

Inclusion Criteria:

Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
Lenvatinib: 7 days
Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent. OR
Uses contraception unless confirmed to be azoospermic
Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, or 30 days after the last dose of lenvatinib, whichever occurs last
Has adequate organ function
Female participants agree to abstain from breastfeeding during the study intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required for each study intervention is:
MK-1308A: 120 days
MK-3475: 120 days
Lenvatinib: 30 days

Exclusion Criteria:

Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
Has current or history of known leptomeningeal involvement
Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
Has an active infection requiring systemic therapy
Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
Has ocular melanoma
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has known history of immunodeficiency virus (HIV)
Has known history of hepatitis B or known hepatitis C virus
Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
Has a history of whole brain irradiation
Has received prior radiotherapy within 2 weeks of first dose of study intervention
Has had major surgery <3 weeks prior to first dose of study intervention
Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
Has had an allogeneic tissue/solid organ transplant