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.

Oncolytic Viral Therapy Using Reovirus

“…The 15 patients who were given reovirus at a dose of 3 × 10 10 TCID50 on days 1-5 on a 28-day cycle were well tolerated. The posttreatment biopsy samples of two patients showed productive reovirus replication as viral antigen coexpression was seen with tubulin despite an increasing NARA response [ 162 ]. Although no objective responses were seen, one patient demonstrated necrotic tissue (75-90 %) in surgically removed lesions that was consistent with treatment effects.…”

“…The results of a phase II trial of intravenous administration of REOLYSIN in patients with metastatic melanoma have been reported recently [ 162 ]. The 15 patients who were given reovirus at a dose of 3 × 10 10 TCID50 on days 1-5 on a 28-day cycle were well tolerated.…”

Evolution of Reovirus in Cancer Therapy

“…[64] Twenty-one patients were injected intravenously with reovirus at a dose of 3×10 10 50% tissue-culture infective dose (TCID 50 ) once every 60 minutes on days 1-5 every 4 weeks, and were monitored for clinical benefits of CR or PR for at least 8 weeks. Although no patients met the criteria for CR or PR, one patient did demonstrate extensive (75%-90%) tumor necrosis in two metastatic lesions following two treatment cycles.…”

Evolution of Reovirus in Cancer Therapy

“…It should be noted that NARAs are prevalent in most adults, owing to exposure to reovirus sometime during their lifetime. [48,[62][63][64] Therefore, future directions need to focus on specifically targeting the antiviral immune response, such as T-cell and B cell responses, without affecting the production of strong antitumor immunity.…”