Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I)

Inclusion Criteria: * Adult patients (≥18 years of age) with histologically or cytologically confirmed metastatic melanoma for which surgery is not recommended with liver metastases; disease must be measurable per RECIST criteria * Patients must have a life expectancy of at least 6 months * Patients must have a performance status of 0 - 2 on the ECOG Performance Scale. * Allowable prior therapy: * Previous adjuvant or neoadjuvant treatment for melanoma is allowed, which may include molecularly-targeted agents, IFN-alpha, ipilimumab, nivolumab, and pembrolizumab, if it was completed at least 6 weeks before enrollment in the study. * Patients who had experienced treatment-related adverse events from prior adjuvant or neoadjuvant treatment for melanoma are allowed if symptoms had returned to baseline or had stabilized. * Prior stereotactic radiotherapy (SBRT) of extrahepatic metastases is permitted. * Patients must be willing to undergo multiple liver tissue biopsies * Patients must have adequate organ function per protocol * Patients must understand and be willing to sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks. * Participants of childbearing potential * Female subject of childbearing potential should have a serum pregnancy within 14 days of enrollment and 72 hours prior to receiving the first dose of I/N, and must be willing to use a highly effective method of contraception for the course of the study through 180 days after the last dose of I/N. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.) * Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 180 days after the last dose of study therapy. Sperm donation is prohibited while on study. (Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.) Exclusion Criteria: * Patients will be excluded from the trial if participants have the following: * Diffuse involvement of liver by cancer on CT, PET, or MRI imaging * More than 4 liver metastases on CT scan at time of initial assessment. If a flare occurs during the initial I/N cycles, up to 8 metastases may be targeted if able to be targeted by a minimum of 8 Gy per fraction while meeting normal tissue constraints. * Diagnosis of underlying parenchymal end stage liver disease (cirrhosis) or biliary disease (primary biliary cirrhosis). * Other locally advanced or metastatic invasive malignancy active within last 3 years, excluding in situ or localized cancers or malignancies which have been treated * Patients who had received previous systemic anticancer therapy for unresectable or metastatic melanoma * Has known active carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). • Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Require daily corticosteroids \>10 mg of prednisone (or its equivalent) * Note: Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would NOT be excluded from the study. * Note: Patients who require the use of topical steroids would not be excluded. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment. * Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or has received a bone marrow transplant or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. * Has a known history of active TB (Bacillus Tuberculosis). * Has known active Hepatitis B or Hepatitis C. * Prior Gr3/4 life threatening immune related adverse event that is considered an unacceptable risk per the treating investigator * Has received a live vaccine within 30 days of enrollment. * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * COVID vaccination acceptable; preferably all doses administered 7 days prior to start of therapy * Lacks insurance preapproval for SBRT