3.1 Registration – Inclusion Criteria
3.11 Age ≥18 years
3.12 Disease characteristics:
3.121 Measurable disease by RECIST v1.1 as defined in Section 11.0
3.122 Confirmed diagnosis of unresectable stage IV metastatic melanoma involving the lungs (at least) that has progressed after at least ONE line of FDA approved therapy (either immune checkpoint inhibitor or targeted therapy) OR relapse of melanoma following/during FDA-approved adjuvant or neo-adjuvant therapy
3.13 The following laboratory values obtained ≤15 days prior to registration:
• Hemoglobin ≥8.0 g/dL
• Absolute neutrophil count (ANC) ≥1500/mm3
• Platelet count ≥75,000/mm3
• Total bilirubin ≤1.5 × ULN
• Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤3.0 × ULN
• Serum creatinine ≤2.0 × ULN
• Calculated creatinine clearance ≥40 ml/min using the Cockcroft-Gault formula

3.14 Pulse oximetry at rest >90% without use of supplemental oxygen
3.15 ECOG Performance Status (PS) 0 or 1 (Appendix I).
3.16 Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only.
3.17 Persons able to become pregnant OR able to father a child must be willing to use an adequate method of contraception while on treatment and for 180 days (6 months) after last treatment dose on this study.
3.18 Provide written informed consent.
3.19a Willingness to provide mandatory blood specimens for correlative research (see Section 14.0).

3.2 Registration - Exclusion Criteria
3.21 Active pulmonary disease requiring ongoing medication NOTE: Stable chronic medication for asthma/COPD is allowed.
3.22 Metastatic uveal melanoma
3.23 Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study
3.24 Active CNS metastases not previously treated. NOTE: Patients with history of previously treated CNS metastases, not demonstrating evidence of progression for at least 8 weeks will be allowed; NOTE: Patients with leptomeningeal metastases are not eligible
3.25 Any of the following prior therapies:
• Allogeneic hematopoietic stem cell transplantation (HSCT)
• Solid organ transplantation
3.26 Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
3.27 Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy. NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
3.28 Active autoimmune disease requiring current systemic treatment with immunosuppressive or immune modulatory agents.
NOTE: Exceptions are allowed for the following conditions:
• Vitiligo
• Resolved childhood asthma/atopy
• Intermittent use of bronchodilators or inhaled steroids
• Daily steroids at dose of ≤10mg of prednisone (or equivalent)
• Local steroid injections
• Stable hypothyroidism on replacement therapy
• Stable diabetes mellitus on therapy (with or without insulin)
• Sjögren’s syndrome
• Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) which is not considered a form of systemic treatment and is allowed

3.29a Known uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring systemic therapy
• Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., Crohn’s disease or others)
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Unstable cardiac arrhythmia or
• Psychiatric illness/social situations that would limit compliance with study requirements (e.g., known substance abuse)
3.29b Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
3.29c History of severe hypersensitivity reactions to sargramostim or monoclonal antibodies.
3.29d Prior history of Grade 4 immune related adverse event (irAE) with prior ICI therapy or failure to recover ( 3.29e Failure to recover from adverse events related to any of the following therapies prior to registration:
• Chemotherapy
• Immunotherapy
• Targeted therapies (e.g., dabrafenib)
• Other investigational agents
• Radiation therapy