Sargramostim (GM-CSF) + PD-1

Inclusion Criteria:

Histologic or cytologic diagnosis of metastatic or unresectable stage III or IV cutaneous melanoma
Prior treatment with immunotherapy
Age ≥ 18 years.
ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

Participants must have normal organ and marrow function as defined below:

leukocytes ≥3,000/mcL
absolute neutrophil count ≥1,500/mcL
platelets ≥100,000/mcL
total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
Measurable disease (by CT, PET/CT or MRI)
The effects of GMCSF and PD-1 inhibition on the developing human fetus are unknown.

For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration.

Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Participants who are receiving any other investigational agents.
Participants with known brain metastases must have documented stability over a four week interval and not be requiring active treatment for these. Prior radiation, surgery and stereotactic radiosurgery are allowed but must be completed four weeks prior to initiating therapy.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab or sargramostim.
Need for systemic steroids at the time of enrollment. Physiologic replacement at a dose of less than 10mg daily prednisone equivalent is allowed.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Participants who are considered Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test in order to be eligible. Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Pembrolizumab, breastfeeding should be discontinued if the mother is treated with Pembrolizumab. These potential risks may also apply to other agents used in this study.
Known active HIV, Hepatitis B or Hepatitis C patients. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for an immunologic effect with the therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
Autoimmune disease that requires treatment at the time of enrollment.