Use of Serial Plasma NGS as a New Efficacy Metric to Guide Immunotherapy Treatment Discontinuation

Inclusion Criteria:

* Adult patients age \> 18) with unresectable, metastatic melanoma (cutaneous, acral, mucosal) or NSCLC who have evidence of disease control after at least 12 months of ICI based therapy (pembrolizumab, nivolumab, nivolumab-relatimab, ipilimumab/nivolumab, atezolizumab, ipilimumab, durvalumab, cemiplimab) with or without chemotherapy in the case of NSCLC. Any line of therapy is permitted with the exception of adjuvant therapy
* Participants must be actively receiving standard of care ICI-based therapy (ICI monotherapy or in combination)
* At time of enrollment patients must have received at least 12months (+/- 4 weeks) from the start of anti-PD-1 therapy and have not experienced a toxicity that prevented them from continuing therapy.
* Participants must have evidence of disease control (stable disease, partial response, or complete response) that is maintained on restaging CT scans or PET CT scans obtained at 12 months (+/- 4 weeks) from the start of initial ICI therapy
* Prior radiation to any site is allowed
* Available tumor tissue (archival) for baseline tissue testing with FoundationOne CDx or previous FoundationOne CDx testing results (within 2 years and prior test results must be after June 30, 2021)
* Life expectancy of greater than 3 months
* Participants with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment are eligible for this trial.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Participants with clinical or radiographic evidence of progressive disease in the 3 months prior to consideration of screening and enrollment
* Participants who are receiving an investigational agent (s)
* Participants who have had ICI discontinued due an immune-related adverse event.
* Patients with a history of an irAE but resumed ICI therapy and are receiving ICI at the time of screening are eligible to enroll.
* Participants on \> 10mg of oral prednisone or its equivalent for treatment of ongoing immune-related toxicity.
* Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia, endocrine toxicity requiring chronic supplementation
* Participants with a concurrent, active malignancy
* Participants in whom F1CDx generation fails
* Participants without available tumor tissue for F1CDx test result or prior F1CDx