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.

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.

PATIENTS AND METHODS:

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.

• Authors: Neeta Somaiah, Matthew S Block, Joseph W Kim, Geoffrey I Shapiro, Khanh T Do, Patrick Hwu, Joseph P Eder, Robin L Jones, Hailing Lu, Jan H Ter Meulen, Chet Bohac, Michael Chen, Frank J Hsu, Sacha Gnjatic, Seth M Pollack
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 19 Pg. 5808-5817 (10 01 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 31227504 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Cancer Vaccines
• Membrane Proteins

Topics

• Adult
• Aged
• Antigens, Neoplasm (biosynthesis, immunology)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Cohort Studies
• Dendritic Cells (cytology, immunology, transplantation)
• Disease-Free Survival
• Female
• Genetic Vectors (administration & dosage, adverse effects, genetics)
• Humans
• Lentivirus (genetics, immunology)
• Male
• Membrane Proteins (biosynthesis, immunology)
• Middle Aged
• Neoplasms (immunology, therapy)
• Sarcoma (immunology, therapy)
• Survival Rate