PV701 is an attenuated, non-recombinant, oncolytic strain of Newcastle disease virus that displays preclinical intravenous (i.v.) efficacy. PV701 selectively lyses tumor cells versus normal cells based on tumor-specific defects in the interferon-mediated antiviral response. In three phase I trials in 113 patients, the effects of dose, schedule and i.v. infusion rate were evaluated. Three types of adverse events were seen: flu-like, tumor-site-specific and those occurring during infusion. The first PV701 dose desensitized the patient to the side effects of further doses, allowing a 5- to 10-fold increase in the maximum-tolerated dose for subsequent doses compared with the first dose. Tumor responses were first noted at the higher doses achieved using desensitization. In 95 evaluable patients, there were ten responses (six major and four minor), with five of these responses occurring in the most recent trial of 18 patients that employed desensitization, high repeat doses and a slower infusion rate. Phase II studies are planned.