Phase I Study of the Intravenous Administration of Attenuated Salmonella typhimurium to Patients With Metastatic Melanoma

The maximum-tolerated dose was 3 × 10 8 cfu/m 2 . Dose-limiting toxicity was observed in patients receiving 1 × 10 9 cfu/m 2 , which included thrombocytopenia, anemia, persistent bacteremia, hyperbilirubinemia, diarrhea, vomiting, nausea, elevated alkaline phosphatase, and hypophosphatemia. VNP20009 induced a dose-related increase in the circulation of proinflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor alpha, IL-6, and IL-12. Focal tumor colonization was observed in two patients receiving 1 × 10 9 cfu/m 2 and in one patient receiving 3 × 10 8 cfu/m 2 . None of the patients experienced objective tumor regression, including those patients with colonized tumors.

The VNP20009 strain of Salmonella typhimurium can be safely administered to patients, and at the highest tolerated dose, some tumor colonization was observed. No antitumor effects were seen, and additional studies are required to reduce dose-related toxicity and improve tumor localization.