Pembrolizumab and High-Dose Recombinant Interferon Alfa-2b before and after surgery in Treating Patients with Locally/Regionally Advanced or Recurrent Melanoma

Inclusion Criteria

• Patients eligible for this study should have locally and/or regionally advanced melanoma that is considered potentially surgically resectable and with biopsiable tumor at baseline
• Be willing and able to provide written informed consent/assent for the trial
• Diagnosis of melanoma belonging to the following American Joint Committee on Cancer (AJCC) TNM stages: * Tx or T1-4 and * N1b, or N2b, or N2c, or N3 and * M0 or M1 (if considered surgically operable)
• Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal and/or in-transit metastasis, or at the time of clinically detected nodal and/or in-transit recurrence and may belong to any of the following groups: * Primary melanoma with clinically apparent (overt) regional lymph node metastases * Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin * Clinically detected primary melanoma involving multiple regional nodal groups * Clinically detected single site of nodal metastatic melanoma arising from an unknown primary * Patients with intransit or satellite metastases with or without lymph node involvement are allowed if they are considered potentially surgically resectable at baseline * Patients with distant metastases with or without intransit or lymph node involvement are allowed if they are considered potentially surgically resectable at baseline ** NOTE: a patient should be determined to be potentially surgically resectable at baseline to be eligible for this neoadjuvant study
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have provided tumor tissue from a newly obtained core, punch, incisional or excisional tumor biopsy; patients must undergo biopsy (core, punch) or open incisional/excisional biopsy (if done as part of a clinically indicated baseline diagnostic procedure) within 4 weeks of registration on the study
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Demonstrate adequate organ function, screening labs that include hematology and chemistry labs should be performed within 14 days of registration on the study
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated* creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN) (glomerular filtration rate [GR] can also be used in place of creatinine or creatinine clearance [CrCl]) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
• 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
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 26 weeks after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 26 weeks after the last dose of study therapy

Exclusion Criteria

• Is currently participating in or has participated in a study of an investigational agent or using 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 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 * 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 * Note: Subjects with hypothyroidism or adrenal insufficiency stable on hormone replacement will not be excluded from the study
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study
• Has evidence of interstitial lung disease or 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 26 weeks after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-programmed cell death 1 ligand 1 (PD-L1), anti-PD-L2, anti-cluster of differentiation 137 (CD137); prior treatment with interferon alfa is allowed; patients with history of allergic or hypersensitivity reaction to interferon alfa are excluded
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B virus 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 prior to the first dose of trial treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current diagnosis of pneumonitis