Pembrolizumab and Sargramostim for the Treatment of Stage III or IV Unresectable or Metastatic Melanoma

Inclusion Criteria

• Histologic or cytologic diagnosis of metastatic or unresectable stage III or IV cutaneous melanoma
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits OR
• Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Measurable disease (by computed tomography [CT], positron emission tomography [PET]/CT or magnetic resonance imaging [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
• Participants may have received any number of prior therapies for treatment of their cutaneous melanoma, excluding prior treatment with sagramostim. Prior therapies may include targeted therapy and immunotherapy (e.g. anti-PD-1). Participants who received prior therapy in the adjuvant, neoadjuvant and metastatic setting will be allowed on study, except those who received sagramostim in any of these settings. Patients must have progressed on prior PD-1 therapy
• 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. Patients may have experienced immunotherapy induced toxicity but must have weaned off steroids or be on less than 10mg daily prednisone equivalent. The treating physician must feel that retreatment with immunotherapy is appropriate and safe based upon type and grade of prior toxicity
• 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 human immunodeficiency virus (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