Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma

Inclusion Criteria:

* Participants must be \>18 years or older.
* Participants must have stage IIIB, IIIC, or IVM1a (equivalent staging at time of enrollment via American Joint Committee on Cancer (AJCC) 7th edition) metastatic melanoma which is eligible for complete surgical resection.
* Prior systemic, regional and radiation anticancer therapies must have been completed at least three months prior to enrollment. Prior therapies (including anti-programmed death (PD)-1 inhibitors) are allowed provided three months have elapsed from last dose.
* Participants must be a candidate for intralesional therapy.
* At least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion \> 10 mm in longest diameter OR
* Multiple injectable melanoma lesions which in aggregate have a longest diameter of \> 10 mm AND
* Must have no known bleeding diathesis or coagulopathy that would make intratumoral injection unsafe.
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Serum (LDH) level \< 1.5 upper limit of normal (ULN) within 28 days prior to enrollment.
* Participants have adequate organ function within 28 days prior to enrollment, as defined in the protocol
* Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 7 months after final nivolumab study treatment.
* Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to the start of treatment.
* Participants must be able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

* Participants with active visceral, central nervous system, or any bone metastases melanoma (Stage IVM1b or IVM1c).
* Participants whose primary diagnosis was ocular melanoma.
* Participants receiving anti-herpes medication (i.e., acyclovir, famciclovir, or valacyclovir) within 1 week prior to initiating HF10 treatment. Participants may not require intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug other than intermittent topical use.
* Participants who have an active herpetic skin lesion(s) or prior complications of herpes simplex virus (HSV)-1 infection.
* 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, as determined by the investigator.
* Medical history of autoimmune disease (e.g. Crohn's disease, ulcerative colitis) or other disease requiring systemic glucocorticoid or immunosuppressive therapy. Subjects who receive daily steroid replacement therapy serve as an exception to this rule. Daily prednisone equivalent at doses up to 10 mg would qualify.
* Participants with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Epstein-Barr Virus (EBV) infection are excluded.
* Pregnant or breast feeding women; women desiring to become pregnant within the timeframe of the study are also excluded.