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

Inclusion Criteria:

- Patients must be >18 years or older.

- Patients must have stage IIIB, IIIC, or IVM1a (equivalent staging at time of
enrollment) 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-PD-1
inhibitors) is allowed provided three months have elapsed from last dose.

- Patients 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

- must have no known bleeding diathesis or coagulopathy that would make intratumoral
injection unsafe.

- Patients 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.

- Patients 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.

- Patients must be able to provide informed consent and willing to sign an approved
consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

- Patients with active visceral, central nervous system, or any bone metastases melanoma
(Stage IVM1b or IVM1c).

- Patients whose primary diagnosis was ocular melanoma.

- Patients receiving anti-herpes medication (i.e., acyclovir, famciclovir, or
valacyclovir) within 1 week prior to initiating HF10 treatment. Patients may not
require intermittent or chronic systemic (intravenous or oral) treatment with an
antiherpetic drug other than intermittent topical use.

- Patients who have an active herpetic skin lesion(s) or prior complications of 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.

- Patients 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.