The first-in-man use of attenuated live Listeria as a cancer vaccine vector was conducted by Advaxis in end-stage (IVb) cervical cancer. The trial demonstrated the safety of this approach, with the side effects being comprised of a flu-like syndrome (fever, chills, headache, etc.) frequently associated with strong innate immune activation. Adverse events responded to over the counter treatments and did not require antibiotics to resolve, further indicating the non-infectious, immune nature of the response. No bacteria were shed in urine or feces and the agent was well tolerated. The patient population tested had advanced metastatic disease and had failed prior cytotoxic therapy. The historical prognosis for this group as determined by the National Cancer Institute is a median survival of 6 months with a one year survival of 5%. As this was the first time this agent was tested in humans, only 2 doses were administered, rather than the 3 dose regimen used to for therapy. Although efficacy was assessed this study, like all phase 1 studies, was not designed or powered to assess efficacy. Nonetheless, in 13 evaluable patients 4 (30%) experienced reductions in their tumor burdens and 3 (23%) are still alive at 3 years post dosing. The one year survival in this study was 53%.
