 This is an international multicenter, open-label, randomized controlled trial RCT of single-agent intralesional PV-10 versus systemic chemotherapy or intralesional oncolytic viral therapy to assess treatment of locally advanced cutaneous melanoma in patients who 1 are not candidates for targeted therapy and 2 are not candidates for an immune checkpoint inhibitor. Subjects in the comparator arm will receive the Investigators choice of dacarbazine DTIC, temozolomide TMZ or intralesional talimogene laherparepvec as determined by Investigator preference and standard of care in the Investigators country or region. Effectiveness will be assessed by comparison of progression-free survival PFS between all intent-to-treat ITT subjects in the two study treatment arms. 