vo and nivolumab vs physician's choice in advanced melanoma that progressed on anti-pd-1 & anti-ctla-4 drugs (ignyte-3)

Conditions: Advanced Melanoma

Summary: this is a randomized, controlled, multicenter, open-label phase 3 clinical study comparing vo in combination with nivolumab versus physician's choice treatment for patients with unresectable stage iiib-iv cutaneous melanoma whose disease progressed on an anti pd-1 and an anti-ctla-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-ctla-4 therapy.


Eligibility criteria:
key inclusion criteria: * male or female who is 12 years of age or older at the time of signed informed consent. * patients with histologically or cytologically confirmed unresectable or metastatic stage iiib through iv/m1a through m1d cutaneous melanoma. * confirmed disease progression (pd) on an approved anti-pd-1 and an anti-ctla-4 treatment, 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 8 weeks 2. patients who in the physician's judgement are not candidates for treatment with an anti-ctla-4 antibody are eligible * has documented braf v600 mutation status. patients with braf mutation should have received prior braf-directed therapy (with or without a mek inhibitor) prior to enrollment in the study, unless deemed not clinically indicated at investigator's discretion due to concurrent medical condition or prior toxicity. * has at least 1 measurable and injectable tumor of ≥1 cm in longest diameter (or shortest 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 activated partial thromboplastin time (aptt) ≤1.5 × uln * eastern cooperative oncology group (ecog) performance status (ps) 0 to 1 for patients 18 years and older or a lansky performance score (psc) ≥80 for patients 12 to 17 years of age. * life expectancy of at least 3 months. * female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least 6 months after the last dose of study treatment. * women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (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 infection requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to dosing. * with active significant herpetic infections or prior complications of hsv-1 infection. * evidence of spinal cord compression or at high risk of spinal cord compression. * known active central nervous system (cns) metastases and/or carcinomatous meningitis at 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 curable cancers 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 current pneumonitis. * prior oncolytic virus or other therapy given by intratumoral administration. * requires intermittent or chronic use of systemic (oral or iv) antivirals with known antiherpetic activity (eg, acyclovir). * has received a live vaccine within 28 days prior to the first dose of study treatment. * 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 of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.