Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma.

Abstract

Reovirus, a replication competent RNA virus, has preclinical activity against melanoma lines and xenografts. We conducted a phase II trial of reovirus in metastatic melanoma patients. Patients received 3 × 10(10) TCID50 on days 1-5 of each 28 day cycle, administered intravenously. Twenty-one eligible patients were enrolled. Treatment was well tolerated without any dose reductions having to be implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15 contained adequate tumor for correlative analysis. In two patients, productive reoviral replication (viral antigen coexpression with tubulin) was demonstrated, despite increase in neutralizing antibody titers. There were no objective responses although 75-90% tumor necrosis, consistent with treatment effect, was observed in one patient who had metastatic lesions surgically removed. Median time to progression and survival were 45 days (range 13-96 days) and 165 days (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was well tolerated in metastatic melanoma patients; viral replication was demonstrated in biopsy samples. Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing.

• Authors: Evanthia Galanis, Svetomir N Markovic, Vera J Suman, Gerard J Nuovo, Richard G Vile, Timothy J Kottke, Wendy K Nevala, Michael A Thompson, Jean E Lewis, Kandelaria M Rumilla, Victoria Roulstone, Kevin Harrington, Gerald P Linette, William J Maples, Matt Coffey, James Zwiebel, Kari Kendra
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 20 Issue 10 Pg. 1998-2003 (Oct 2012) ISSN: 1525-0024 [Electronic] United States
• PMID: 22871663 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• KRAS protein, human
• Proto-Oncogene Proteins
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Administration, Intravenous
• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Male
• Mammalian orthoreovirus 3 (physiology)
• Melanoma (secondary, therapy)
• Middle Aged
• Neoplasm Metastasis
• Oncolytic Virotherapy (methods)
• Proto-Oncogene Proteins (genetics, metabolism)
• Proto-Oncogene Proteins B-raf (genetics, metabolism)
• Proto-Oncogene Proteins p21(ras)
• Virus Replication
• Young Adult
• ras Proteins (genetics, metabolism)