Imiquimod and Pembrolizumab in Treating Patients With Stage IIIB-IV Melanoma

Inclusion Criteria

• Histological confirmation of stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c that is not suitable for surgical resection
• Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies for their metastatic disease
• At least one cutaneous lesion that is amenable to treatment with topical imiquimod
• Measurable disease by RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin > 9.0 g/dL or >= 5.6 mmol/L without transfusion or (EPO) erythropoietin dependency (within 7 days of assessment)
• Serum total bilirubin = 1.5 ULN
• Aspartate transaminase (AST) = = 2.5mg/dL
• International normalized ratio (INR) or prothrombin time (PT) = = 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
• Negative urine or serum pregnancy test done = 1 year; male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; abstain from heterosexual activity is also acceptable method of contraception for males
• 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
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• 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
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm or used an investigational device =< 4 weeks from registration
• History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks prior to registration
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy =< 2 weeks prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Known secondary malignancy that has progressed within the last 3 years or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s parti