A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial

Inclusion Criteria

1. Age 18 years or older
2. Newly diagnosed locally advanced squamous cell carcinoma of cervix (FIGO 2018 stage IB3-IVA with primary tumor ≥ 5 cm and/or positive pelvic or periaortic nodal disease assessed by imaging).
3. Histologic diagnosis of squamous cell carcinoma of the cervix.
4. Written informed consent before initiation of any study-related procedures;
5. WHO/ECOG performance status 0-2.
6. Adequate liver (ALT, AST, Alk Phos and total Bili ≤ 2-fold the upper limit of normal), and renal functions (Creatinine ≤ 1.5).
7. Absence of current malignancies at other sites, except for adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors who have undergone potentially curative therapy for a prior malignancy who have no evidence of that disease for 5 years and who are deemed at low risk for recurrence are eligible for the study

Exclusion Criteria:

1. HIV infection, cellular immune deficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
2. Prior diagnosis of hepatitis B or C (unless anti-hepatitis C therapy has produced a sustained virologic response);
3. History of clinically significant autoimmune disease, Crohn's disease, or ulcerative colitis
4. Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the Investigator.
5. Receipt of immunotherapy (e.g., IFNs, check-point inhibitors, tumor necrosis factor, interleukins, etc.) or biological response modifiers (GM-CSF, granulocyte colony-stimulating factor, macrophage colony-stimulating factor) within 4 weeks before the first study vaccination.
6. Receipt of chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

   • Current or recent use of physiologic doses of intra-articular, topical, or inhaled corticosteroids is acceptable.
7. History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines \[e.g., Silgard®, Cervarix®, Gardasil®\] are not excluded)
8. Known or suspected hypersensitivity to any component of the investigational product or contraindications to cisplatin (e.g., peripheral neuropathy grade ≤ 2 or ototoxicity ≤grade 2 per CTCAE v5.0)
9. Previous pelvic RT.
10. Previous chemotherapy for the cervix tumor
11. Previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy
12. Prior major surgery within 4 weeks of enrollment from which the patient has not recovered
13. Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results
14. Concurrent participation in another therapeutic investigational study or use of another investigational drug within 6 months before the first study vaccination
15. Previous enrollment in this study
16. HPV genotyping is to be done from cervical swab samples. Enrollment will not require HPV testing.
17. Pregnancy: a female subject defined as a WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.