VO and Nivolumab vs Physician's Choice in Advanced Melanoma That Progressed on Anti-PD-1 & Anti-CTLA-4 Drugs (IGNYTE-3)

Key Inclusion Criteria:

• Male or female who is 12 years of age or older at the time of signed informedconsent.

• Patients with histologically or cytologically confirmed unresectable or metastaticStage IIIb through IV/M1a through M1d cutaneous melanoma.

• Confirmed disease progression (PD) on an approved anti-PD-1 and an anti-CTLA-4treatment, administered either as a combination regimen (eg, nivolumab + ipilimumab)or in sequence.

1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8weeks

2. Patients who in the physician's judgement are not candidates for treatment withan anti-CTLA-4 antibody are eligible

• Has documented BRAF V600 mutation status. Patients with BRAF mutation should havereceived prior BRAF-directed therapy (with or without a MEK inhibitor) prior toenrollment in the study, unless deemed not clinically indicated at Investigator'sdiscretion due to concurrent medical condition or prior toxicity.

• Has at least 1 measurable and injectable tumor of ≥1 cm in longest diameter (orshortest diameter for lymph nodes).

• Has adequate hematologic function.

• Has adequate hepatic function.

• Has adequate renal function.

• Prothrombin time (PT) ≤1.5 × ULN and partial thromboplastin time (PTT) or activatedpartial thromboplastin time (aPTT) ≤1.5 × ULN

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 forpatients 18 years and older or a Lansky performance score (PSc) ≥80 for patients 12to 17 years of age.

• Life expectancy of at least 3 months.

• Female and male patients of reproductive potential must agree to avoid becomingpregnant or impregnating a partner and adhere to highly effective contraceptionrequirements during the treatment period and for at least 6 months after the lastdose of study treatment.

• Women of childbearing potential must have a negative serum beta-human chorionicgonadotropin (β-hCG) test within 72 hours before the first dose of study treatment.

Key Exclusion Criteria:

• Primary mucosal or uveal melanoma.

• More than 2 lines of systemic therapy for advanced melanoma.

• Known acute or chronic hepatitis.

• Known human immunodeficiency virus (HIV) infection.

• Active significant herpetic infections or prior complications of HSV-1 infection.

• Had systemic infection requiring IV antibiotics or other serious active infectionrequiring antimicrobial, antiviral, or antifungal treatment within 14 days prior todosing.

• With active significant herpetic infections or prior complications of HSV-1infection.

• Evidence of spinal cord compression or at high risk of spinal cord compression.

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitisat time of screening.

• Serum lactate dehydrogenase (LDH) >2 × ULN.

• Major surgery ≤2 weeks prior to starting study drug.

• Prior malignancy active within the previous 3 years, except for locally curablecancers that have apparently been cured

• History of significant cardiac disease including myocarditis or congestive heart.

• History of life-threatening toxicity related to prior immune.

• Active, known, or suspected autoimmune disease requiring systemic treatment.

• History of (noninfectious) pneumonitis that required steroids or has currentpneumonitis.

• Prior oncolytic virus or other therapy given by intratumoral administration.

• Requires intermittent or chronic use of systemic (oral or IV) antivirals with knownantiherpetic activity (eg, acyclovir).

• Has received a live vaccine within 28 days prior to the first dose of studytreatment.

• Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose,whichever is shorter.

• Conditions requiring treatment with immunosuppressive doses (>10 mg per day ofprednisone or equivalent) of systemic corticosteroids other than for corticosteroidreplacement therapy within 14 days after enrollment.