Intralesional Influenza Vaccine for the Treatment of Stage I-III and IV Melanoma

Inclusion Criteria

• Males or females
• 18 to 99 years of age
• Histologically confirmed cutaneous melanoma by historical pathology report review, clinical stage I-III (Cohort #1), or stage IV (Cohort #2) cutaneous melanoma
• At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring >= 1 cm by digital caliper (with digital photography documentation) or ultrasound (with ultrasound image documentation)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Absolute neutrophil count (ANC) >= 1.5 x 10^3/mm^3 (drawn at or not more than 30 days prior to the screening visit)
• Hemoglobin (Hgb) >= 9 g/dL (drawn at or not more than 30 days prior to the screening visit)
• Platelet count >= 100 x 10^3/mm^3 (drawn at or not more than 30 days prior to the screening visit)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) or =< 5 x ULN in patients with liver metastases (Cohort 2 only) (drawn at or not more than 30 days prior to the screening visit)
• Prothrombin time =< 1.5 x ULN (drawn at or not more than 30 days prior to the screening visit)
• Total bilirubin =< 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with known Gilbert syndrome) (drawn at or not more than 30 days prior to the screening visit)
• Creatinine clearance of >= 50 ml/min by Cockcroft-Gault equation (drawn at or not more than 30 days prior to the screening visit)
• Women of childbearing potential (WOCBP) must agree to use effective contraceptive methods from screening until at least: * Cohort 1: 14 days after the surgical resection for subjects in Cohort 1 * Cohort 2: ** Nivolumab: 5 months after the last dose of either nivolumab or intralesional Flucelvax, whichever is later ** Pembrolizumab: 4 months after the last dose of either pembrolizumab or intralesional Flucelvax, whichever is later ** Ipilimumab: 3 months after the last dose of either ipilimumab or intralesional Flucelvax, whichever is later ** Relatlimab + nivolumab (marketed under the trade name Opdualag): 5 months after the last dose of either Opdualag or intralesional Flucelvax, whichever is later. ** Combination ipilimumab with other checkpoint inhibitor: Whichever is later: *** 3 months after the last dose of either ipilimumab or intralesional Flucelvax *** Above-bulleted recommendation for nivolumab or pembrolizumab
• Non-childbearing potential is defined as a woman who meets either of the following criteria: a) postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy
• Effective contraception methods are defined as one of the following: * True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject * Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception * Condoms and spermicide * Diaphragm and spermicide * Oral or implanted hormonal contraceptive * An intra-uterine device
• WOCBP must have a negative pregnancy test (serum or urine)

Exclusion Criteria

• Known allergy or intolerance to influenza vaccination
• Subjects with condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration
• Active, known or suspected autoimmune disease
• Active brain metastasis or leptomeningeal metastasis
• Diagnostic biopsy of ocular or mucosal melanoma
• Any melanoma therapy within 6 months of enrollment, though prior surgical resection is permitted
• Incarcerated patients
• Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to randomization: stable and adequate CD4 counts (≥ 350 mm^3), and serum HIV viral load of < 25,000 IU/ml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria
• Pregnant or lactating patients
• Patients incapable of independently providing consent