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Clin Cancer Res. 2019 Jun 21. doi: 10.1158/1078-0432.CCR-19-1025. [Epub ahead of print]

First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1.

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Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut.
Early Drug Development Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
Division of Oncology, University of Washington, Seattle, Washington.
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Immune Design Corp., Seattle, Washington and South San Francisco, California.
Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.


Purpose: LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1-expressing tumors. This phase I 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: 108 vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 108 vg, 109 vg, 1010 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.

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