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- Title
378. Phase I Trial of Intravenous Infusion of Onyx 015 and Enbrel in Solid Tumor Patients.
- Authors
Edelman, Gerald; Senzer, Neil; Nemunaitis, Michael; Cunningham, Casey; Sovern, Paige; Tong, Alex; Nemunaitis, John
- Abstract
Onyx 015 is an E1B deleted conditional replicating adenovirus which has demonstrated control of local regional disease in prior studies [E. Lin and J. Nemunaitis, Cancer Gene Ther 11, 643 (2004)] but demonstrates limited effect when administered as an intravenous therapeutic. We hypothesized that systemic activity may be potentiated by reduction of viral clearance related to tumor necrosis factor a (TNFα).We report here results of a phase 1 dose-escalation trial of intravenous infusion, Onyx-015 in combination with a fixed dose of Enbrel (soluble TNFα receptor). Nine patients with advanced malignancies and extensive prior treatment were treated with an escalating dose of virus. Four patients, were treated at a dose level of 1 x 1010 viral particles, 3 patients at 1 x 1011, and two patients at 1 x1012 (1x/week x 3 weeks per cycle). Accrual at the 1 x 1012 dose level is continuing. Each patient received a fixed dose of Enbrel at 25 mg via subcutaneous injection during cycle 1 (2x/week starting 1 week before Onyx 015 then for 3 weeks after in cycle 1 only). Treated patients included 2 with breast cancer, 4 colorectal cancer, 1 lung cancer, 1 endometrial cancer, and 1 ovarian cancer. Ages ranged from 41 to 78 years with a mean of 62. Eighty total intravenous infusions of virus were administered. At the 1 x 1010 viral dose, one patient experienced grade 2 myalgias, fatigue, and dyspnea and two patients experienced grade 3 hyponatremia. At the 1 x 1011 viral dose, one patient experienced grade 3 elevation of alkaline phosphatase, hypoalbuminemia, and grade 4 anemia. Toxicities were felt to be unrelated to Onyx 015. There have been no treatment related toxicities at the 1 x 1012 viral particle dose. In conclusion, Onyx 015 given as an intravenous infusion appears well tolerated when administered in combination with enbrel. Follow up clinical results will be presented, additionally pharmacokinetic and neutralizing antibody response will be compared between cycle 1 (with enbrel) and cycle 2 (without enbrel).Molecular Therapy (2006) 13, S144–S144; doi: 10.1016/j.ymthe.2006.08.438
- Subjects
CANCER patients; CANCER treatment; INTRAVENOUS therapy; LUNG cancer; COLON cancer; TUMOR necrosis factors
- Publication
Molecular Therapy, 2006, Vol 13, pS144
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.438