An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+

Worldwide, many women carry HPV and cervical cancer is the leading cancer killer of women
under the age of 50. Although its consequences are considerably less severe in the US, it
leads to considerable morbidity. Many published clinical trials describe the
immunotherapeutic treatment of early stage, pre-invasive, cervical cancer. It is widely
recognized that immunotherapies are most effective in early stage disease because the immune
system is least debilitated and disease burden is lowest. Invasive cervical cancer is
preceded by a long, slowly progressive, pre-invasive phase termed Cervical Intraepithelial
Neoplasia (CIN), which allows for this therapeutic approach. An ideal therapy would result
in the remission of CIN 2/3 without damage to cervical tissue. A National Institute of
Cancer panel charged with achieving consensus on this issue concluded that a non-surgical
medical treatment for this indication would be valuable

The primary objectives of this trial are to test three doses of Lovaxin C to determine if
vaccination with Lovaxin C in women with CIN 2/3 for whom surgery is indicated can safely
reverse the disease compared to placebo treated control patients.

An earlier Phase 1/2 trial of Lovaxin-C in late stage metastatic cervical cancer used a
regimen of two doses given with a 28-day interval. That regimen was shown to be safe and to
generate reduction in tumor burdens in some patients. In this trial we will treat earlier
stage disease in healthier patients with better immune systems, will use the same and lower
doses as given before, but add an additional dosing to the regimen by administering the
lowest dose that we assessed previously and by adding a third vaccination to the prior
regimen. Unlike the phase 1 trial in which 2 doses were given with a 3 week separation,
dosing in the proposed trial will be separated by 4-week intervals.

Inclusion Criteria:

- Histologically confirmed CIN 2/3 that requires surgical intervention

Exclusion Criteria:

- Previous history of listeriosis

- Steroid use

- Antibiotic use

- Negative anergy panel

- HIV positive

- Pregnant or actively trying during the treatment period

- Intercurrent disease