A phase i study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors

John Nemunaitis, Alex W. Tong, Michael Nemunaitis, Neil Senzer, Anagha P. Phadke, Cynthia Bedell, Ned Adams, Yu An Zhang, Phillip B. Maples, Salina Chen, Beena Pappen, James Burke, Daiju Ichimaru, Yasuo Urata, Toshiyoshi Fujiwara

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Abstract

A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 × 10 10, 1 × 10 11, 1 × 10 12 viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.

Original languageEnglish
Pages (from-to)429-434
Number of pages6
JournalMolecular Therapy
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 1 2010

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Nemunaitis, J., Tong, A. W., Nemunaitis, M., Senzer, N., Phadke, A. P., Bedell, C., Adams, N., Zhang, Y. A., Maples, P. B., Chen, S., Pappen, B., Burke, J., Ichimaru, D., Urata, Y., & Fujiwara, T. (2010). A phase i study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Molecular Therapy, 18(2), 429-434. https://doi.org/10.1038/mt.2009.262