PURPOSE: LV305 is a modified, third generation, non-replicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo LV305 induces expression of the NY-ESO-1 cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1-expressing tumors. This phase 1 study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors. EXPERIMENTAL DESIGN: Adults with previously-treated, advanced, NY-ESO-1-positive solid tumors and limited tumor burden were eligible. LV305 was administered every 3 weeks by intradermal injection in four dose cohorts (Cohort 1: 10(8) vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 10(8) vg, 10(9) vg, 10(10) vg x 4 doses). RESULTS: Thirty-nine patients were enrolled: 3 patients each in Cohorts 1, 1A, and 2, and 30 patients in Cohort 3. No dose-limiting toxicities were observed. Tumor types included sarcoma (n=24), ovarian (n=8), melanoma (n=6), and lung cancer (n=1). All treatment-related adverse events were grade 1 or 2. Common treatment-related adverse events were fatigue (49%), injection-site reactions (46%), and myalgia (21%). The disease control rate was 56.4% in all patients and 62.5% in sarcoma patients. One patient with synovial sarcoma achieved a partial response lasting >36 months. Anti-NY-ESO-1-specific CD4(+) and/or CD8(+) T cells were induced in 57% of evaluable sarcoma patients. Induction of an anti-NY-ESO-1 immune response was associated with improved 1-year survival in an exploratory analysis. CONCLUSIONS: This first-in-class, first-in-human study of LV305 demonstrated a favorable safety profile, induction of antigen-specific responses, and potential clinical activity in patients with advanced cancer.