FUSA With Intratumoral PolyICLC in Regionally Advanced Resectable Melanoma

Inclusion Criteria: 1. Age ≥18 years. 2. Diagnosis of advanced melanoma planned for surgical resection. 3. Focused Ultrasound Ablation (FUSA): The targeted lesion(s) must be visible by ultrasound imaging and meet the following criteria. Note: Brain lesions may not be targeted for treatment. 1. Approximately 1 cm (or more) diameter of treatable tumor volume for lesions to be treated with FUSA. 2. The target treatment area needs to be contained within a region at least 5 mm from the skin surface and less than or equal to 23 mm from the skin surface. The target treatment area must be at a safe distance from all critical structures, including but not limited to ribs or other bony structures, vital organs, named blood vessels or nerves. 3. The critical structures, with the exception of the skin, will not be in the pre-focal ultrasound path. This will be considered at enrollment and confirmed immediately prior to treatment. 4. The anterior-posterior dimension of the treatment area by US should be no less than 9 mm. 4. A subjects target lesion must be amenable to intratumoral injection with polyICLC per the treating clinician's discretion. 5. Subjects must be receiving checkpoint blockade (either monotherapy or combination therapy) at the time of registration. 6. Biopsies: Note: Biopsies may be completed with or without image guidance. Lesions that have been selected for focused ultrasound may have been previously radiated provided: * The tumor site that was previously radiated has progressed. * A baseline biopsy of the tumor site is obtained following progression and prior to study entry. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 8. Subjects with known brain metastases may participate if all of the following are true: * There has been no evident growth of any brain metastasis since the most recent treatment * No brain metastasis is \> 2 cm in diameter at the time of registration. * Neurologic symptoms have returned to baseline, * There is no evidence of new or enlarging brain metastases, * Subjects are not using steroids for at least 7 days prior to registration, except as allowed in Section 5.2. Regardless of dose, however, subjects who are on a steroid taper for management of brain metastases are not eligible until 7 days after completion of that steroid taper. 9. Ability and willingness to give informed consent. Exclusion Criteria: 1. Any of the following medications or treatments are administered to the subject within 4 weeks of study day 1: 1. Radiation therapy (Note: Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week prior to registration) 2. Allergy desensitization injections 3. High doses of systemic corticosteroids, with the following qualifications and exceptions: * Daily doses of 10 mg or less prednisone (or equivalent) per day administered parenterally or orally are allowed in patients with normal adrenal and pituitary function. * In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed. * Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent) 41,42 * Topical and nasal corticosteroids are acceptable. 4. Growth factors (e.g. Procrit®, Aranesp®, Neulasta®) 5. Interleukins (e.g. Proleukin®) 6. Any investigational therapeutic agent. 7. Targeted therapies specific for mutated BRAF or for MEK 8. Live vaccine 9. Interferon (e.g. Intron-A®) 10. Cytotoxic chemotherapy for cancer 2. Subject has a known addiction to alcohol or drugs and is actively taking those agents, or has recently (within 1 year) taken these agents or has ongoing illicit IV drug use. 3. Subject is known to be HIV positive or has evidence of active Hepatitis B or C virus, unless: * The subject has HIV but has been taking antiretroviral therapy, and agrees to take antiretroviral therapy throughout the study * The subject has active Hepatitis B or C but does not have a detectable viral load 4. Pregnancy or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test (urinary or serum beta-HCG) obtained within 2 weeks prior to registration. Males and females must agree, in the consent form, to use effective birth control methods during the course of treatment and following treatment in accordance with the labeling guidelines for each approved therapy. 5. Medical contraindications or potential problems that prevent compliance with the requirements of the protocol in the opinion of the investigator. 6. Active infection requiring systemic therapy. 7. The presence of Class III or IV heart disease as classified according to the New York Heart Association. 8. Previous treatment with polyICLC within 4 weeks. If a subject was previously treated with intratumoral polyICLC and experienced a significant (grade ≥3) toxicity related to the polyICLC treatment, the tumor that was treated should not be re-treated as part of this protocol.