Study of TLR9 Agonist Vidutolimod (CMP-001) in Combination with Nivolumab Vs. Nivolumab

Inclusion Criteria: 1. Be willing and able to provide written informed consent for the study. 2. Be ≥ 18 years of age on day of signing informed consent. 3. Willingness to undergo \[18F\]F-AraG PET imaging at pre- and week 3 timepoints. 4. Diagnosis of histologically or cytologically confirmed diagnosis of cutaneous melanoma belonging to one of the following AJCC TNM stages: 1. Tx or T1-4 and 2. N1b, or N1c, or N2b, or N2c, or N3b, or N3c and 3. M0 Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal metastasis; or at the time of clinical detected nodal recurrence; and may belong to any of the following groups: * Primary cutaneous melanoma with clinically apparent regional lymph node metastases. * Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin. * Clinically detected primary cutaneous melanoma involving multiple regional nodal groups. * Clinical detected nodal melanoma (if single site) arising from an unknown primary. * In-transit and/or satellite metastases with regional lymph node involved permitted if considered potentially surgically resectable at baseline. * NOTE: Patients whose sole site of disease is regional lymph node involvement of the parotid LN basin are not eligible for this neoadjuvant study. * NOTE: Patients with only in-transit and/or satellite metastases without regional lymph node involvement are not eligible for this neoadjuvant study. * NOTE: Determination of potential resectability must be made at baseline to be eligible for this neoadjuvant study. * NOTE: Patients with mucosal and/or uveal melanoma are not permitted to enroll. Patients with melanomas of unknown primary may be enrolled at the discretion of the treating investigator in discussion with Principal Investigator. 5. Presence of injectable and measurable disease based on RECIST 1.1. 6. Willing to undergo tumor biopsy (core, punch, incisional or excisional). Patients must undergo biopsy (core, punch) or open biopsy (incisional, excisional) within 4 weeks of registration on the study and at W4-5. 7. Performance status of 0 or 1 on the ECOG Performance Scale. 8. Demonstrate adequate organ function as defined below performed on screening labs obtained within 4 weeks of registration. * Absolute neutrophil count (ANC) ≥1,500 /mcL * Hemoglobin ≥9 g/dL or ≥5.6 mmol/L * Platelets ≥100,000 / mcL * Serum creatinine or Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN. * Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN. * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN. * International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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. * 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. 9. 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. 10. 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 (Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 11. 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: 1. History of uveal or mucosal melanoma. 2. 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. 3. 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. 4. 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 autoimmune disorders of Grade 4 while on prior immunotherapy will be excluded. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤1 and the subject has been off systemic steroids at doses \>10 mg/d for at least 2 weeks. 5. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases. 6. 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. 7. Has a systemic disease that requires systemic pharmacologic doses of corticosteroids greater than 10mg daily prednisone (or equivalent). Subjects who are currently receiving steroids at a dose of ≤10mg daily do not need to discontinue steroids prior to enrollment Subjects that require topical, ophthalmologic and inhalational steroids would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. Subjects who require active immunosuppression (greater than steroid dose discussed above) for any reason are excluded. 8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis. 9. Has an active infection requiring systemic therapy. 10. 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. 11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 12. 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. 13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or BRAF/MEK inhibitor. Prior treatment with ipilimumab or interferon alfa is allowed. Patients with history of allergic or hypersensitivity reaction to interferon alfa or ipilimumab are also excluded. 14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected. Patients with treated Hepatitis B/C with no evidence of active infection may be enrolled.