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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.

Author information

1
Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas. nsomaiah@mdanderson.org.
2
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
3
Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut.
4
Early Drug Development Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
6
Division of Oncology, University of Washington, Seattle, Washington.
7
Fred Hutchinson Cancer Research Center, Seattle, Washington.
8
Immune Design Corp., Seattle, Washington and South San Francisco, California.
9
Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Abstract

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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