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

Prior treatment

• Prior diagnosis of hepatitis B or C (unless anti-hepatitis C therapy has produced a sustained virologic response);
• Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the Investigator.
• 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.
• 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.
• History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines \[e.g., Silgard®, Cervarix®, Gardasil®\] are not excluded)
• 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)
• Previous pelvic RT.
• Previous chemotherapy for the cervix tumor
• Previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy
• Prior major surgery within 4 weeks of enrollment from which the patient has not recovered
• Other condition or prior therapy that, in the opinion of the Investigator, compromises the subject's welfare or may confound study results
• Concurrent participation in another therapeutic investigational study or use of another investigational drug within 6 months before the first study vaccination
• Previous enrollment in this study

Other illness

• HIV infection, cellular immune deficiencies, hypogammaglobulinemia or dysgammaglobulinemia, or hereditary or congenital immunodeficiencies
• History of clinically significant autoimmune disease, Crohn's disease, or ulcerative colitis

Lab values

• 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.

Other

• HPV genotyping is to be done from cervical swab samples. Enrollment will not require HPV testing.

• Age 18 years or older
• 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).
• Histologic diagnosis of squamous cell carcinoma of the cervix.
• Written informed consent before initiation of any study-related procedures;
• WHO/ECOG performance status 0-2.
• Adequate liver (ALT, AST, Alk Phos and total Bili ≤ 2-fold the upper limit of normal), and renal functions (Creatinine ≤ 1.5).
• 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