Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent
Histologically confirmed, unresectable or metastatic melanoma, and refractory or relapse after PD1 antibody treatment and ineligible for other standard of care therapy
ECOG Performance scale of 0-2
Life expectancy of equal to or greater than 3 months
Adequate bone marrow and organ functionAdequate
Any prior systemic MDM2-p53 inhibitor treatment Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to first dose.
Prior loco-regional treatment with intralesional therapy (e.g. talimogene laherparepvec) for unresectable or metastatic melanoma in the last 6 months prior to start of study treatment.
Received hormonal and biologic (<1 half-lives), small molecule targeted therapies or other anti-cancer therapy within 21 days prior to first dose Radiation or surgery within 14 days of study entry, thoracic radiation within 28 days prior to first dose.
Has known active central nervous (CNS) metastases and/or carcinomatous meningitis. Or has neurologic instability per clinical evaluation due to tumor involvement of the CNS.
Requirement for corticosteroid treatment, with the exception of megestrol, local use of steroid: i.e.: topical corticosteroids, inhaled corticosteroids for reactive airway disease, ophthalmic, intraarticular, and intranasal steroids.

Pathologically documented unresectable melanoma, American Joint Committee on Cancer (AJCC) version 8, Stage III or IV
Subjects must be refractory to anti-PD-1 monoclonal antibodies (pembrolizumab or nivolumab either as monotherapy or in combination with other approved checkpoint inhibitors or targeted therapies according to their approved label
Resolution/improvement of anti-PD1 mAb-related AEs (including immune related AEs; irAEs) back to Grade 0-1
BRAF V600 mutation-positive melanoma could have received standard of care targeted therapy for advanced or metastatic disease
Has a performance status of 0 or 1 on the ECOG Performance Scale
Subject has disease that is suitable for local therapy administered with curative intent
Clinically active CNS metastases
Subject with a diagnosis of uveal melanoma
Subject who had an allogenic tissue/solid organ transplant
Subjects with electronic pacemakers or defibrillators

Age >=18 years.
Participants must be newly diagnosed, treatment-naive with histologically confirmed stage IIIC unresectable melanoma or stage IV melanoma.
Have measurable disease per RECIST v1.1
Have an ECOG performance status 0-1
Participants who have received previous immunotherapy for any cancer (excluding melanoma) including PD-1/PD-L1 inhibitors but not interferons and CTLA-4 inhibitors.
Participants with chronic autoimmune diseases
Other invasive cancers diagnosed < 3 years back that required systemic treatment. If diagnosed with other invasive cancer ≥ 3 years, should have complete recovery from all systemic toxicity except neuropathy and alopecia

Patient must be ≥ 18 years of age.
Patient must have active advanced melanoma, defined as unresectable stage IIIB-IV by AJCC 8th edition
Patient must have an ECOG performance status of 0-2
Patient must have completed an FDG-PET/CT scan at week 52 (+/- 2 weeks) from start of initial anti-PD-1 therapy
For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable
Patient must not have brain metastases
Women must not be pregnant or breast-feeding
Patient must not be receiving concurrent anti-tumor therapies in addition to the standard of care anti-PD-1 regimens

Prior treated central nervous system (CNS) metastases must have magnetic resonance imaging (MRI) evidence of no recurrence for at least 4 weeks after treatment
Male or female patients age 12 years or older at the time of signing the informed consent form (ICF) (age 18 years or older where local regulations or institutional policies do not allow for patients < 18 years of age to participate).
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologically confirmed Stage IIIA (LN metastasis > 1 mm [i.e., at least one LN metastasis measuring > 1 mm at greatest diameter]), IIIB/C/D, or IV (M1a/b/c/d) cutaneous melanoma by AJCC
Tumor tissue from biopsy or resected disease must be provided to central laboratory for PD-L1 status analysis
Use of an investigational agent or an investigational device within 28 days before randomization
History of ocular/uveal melanoma or mucosal melanoma
Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
Prior therapy for melanoma
History of leptomeningeal disease