Pembrolizumab and Tretinoin in Treating Patients with Stage III-IV Melanoma

Inclusion Criteria

• Diagnosis of advanced melanoma (unresectable stage III or stage IV melanoma)
• Planned standard treatment with pembrolizumab
• Be willing and able to provide written informed consent for the trial
• State willingness to comply with all study procedures and be available for the duration of the trial
• Be >= 18 years of age on day of signing informed consent
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment initiation)
• Platelets >= 100,000/mcL (performed within 10 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated (creatinine clearance should be calculated per institutional standard) creatinine clearance >= 60 mL/min for patient with creatinine levels > 1.5 X institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
• Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation)
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Male subjects of childbearing potential must 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 * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent; subjects with chronic conditions such as vision changes from plaque radiation therapy for ocular melanoma or prior hearing loss that is not reasonably expected to be exacerbated by the investigational product may be included * 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
• Has a known additional malignancy that is progressing 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
• Has 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a live vaccine within 30 days of planned start of study therapy * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Has known sensitivity to retinoic acid derivatives
• Has a medical history of allogenic stem cell transplant or received a solid organ transplant