Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: Safety, feasibility and biological activity

J. Nemunaitis, C. Cunningham, A. Buchanan, A. Blackburn, G. Edelman, P. Maples, G. Netto, A. Tong, B. Randlev, S. Olson, D. Kirn

Research output: Contribution to journalArticlepeer-review


Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 × 1010 to 2 × 1013 particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, γ-IFN, TNF-α and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses ≥2 × 1012 particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 × 1013 particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.

Original languageEnglish (US)
Pages (from-to)746-759
Number of pages14
JournalGene Therapy
Issue number10
StatePublished - 2001


  • Adenovirus
  • ONYX-015
  • Replication

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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