A Pilot Study of ctDNA-Guided Immune Checkpoint Inhibitor Duration in Patients With Advanced Melanoma.

Inclusion Criteria: 1. Age \> 18 with any subtype of unresectable stage III or stage IV melanoma treated with anti-PD-1-based ICI which includes both anti-PD-1 monotherapy and dual checkpoint inhibitor regimens such as ipilimumab plus nivolumab and nivolumab plus relatlimab. Disease control after at least 6-12 months of anti-PD-1-based ICI defined as a radiographic RECIST CR, PR, or SD and planned for at least 1 year of treatment OR Development of an irAE(s) on an anti-PD-1-based regimen requiring treatment interruption and immunosuppression where the investigator is considering treatment discontinuation. Patients must have a radiographic RECIST PR or CR at the treatment duration decision time point. 2. Any line of therapy, with the exception of adjuvant therapy. 3. Ability to understand and the willingness to sign a written informed consent document. 4. Patients with brain metastasis may be included only if there was also presence of extracranial disease. 5. ECOG performance status 0-2. Exclusion Criteria: 1. Participants who are receiving investigational therapies. 2. Inadequate tumor quantity or quality to conduct initial Signatera ctDNA testing. 3. Intracranial-only metastatic melanoma. 4. Patients with best response of progressive disease at time of screening. 5. Patients who have had their melanoma completely surgically resected such that response to immunotherapy is no longer evaluable. 6. Patients who are unwilling to continue or stop ICI therapy using ctDNA guidance in combination with imaging response. 7. History of a life-threatening or severe irAE that would make ICI rechallenge unsafe. These cases will be discussed with the Principal Investigator. 8. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.