A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer

A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer

The aim of this study is to assess the potential benefit of the addition of immunotherapy with VGX-3100 and INO-9012 (i.e. INO-3112) to concomitant CRT or, to concomitant CRT and continued as adjuvant in patients with locally advanced cervical cancer.

Safety run-in: To test the safety of CRT combined with immunotherapy with INO-3112. This safety run-in phase will include the first 3 patients treated in each of the two INO-3112 combination arms who are exposed to at least two immunotherapy doses and evaluate whether the combination does not pose undue immediate risks to the patients further enrolled in the trial.

Phase II:To demonstrate sufficient activity in the experimental combination arms to warrant a further phase III conclusive trial based on progression free survival (PFS) at 18 months assessed by RECIST by the local investigator. The efficacy will be assessed within each experimental arm while the standard arm will serve as a reference arm to check the reliability of the results.

Main inclusion criteria:

Registration step

• Age 18 years or older;
• Newly diagnosed locally advanced cervical cancer defined as FIGO 2009: stage IB2, IIA&IIB, IIIA&IIIB or IVA disease;
• No evidence of distant metastases (Stage IVB);
• Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix is accepted. Not accepted are small cell, clear cell and other rare variants of the classical adenocarcinoma;
• Availability of HPV 16 and HPV 18 testing;
• No HIV seropositive, Hepatitis B or C (unless sustained virologic response achieved by anti-HCV therapy);
• Written informed consent must be given according to ICH/GCP, and national/local regulations

Randomization step

• Positive for HPV 16 and/or HPV 18 as assessed by central lab;
• WHO/ECOG performance status 0 - 2
• Adequate hematological, liver and renal functions
• ECG with no clinically significant findings as assessed by the investigator performed within 30 days of signing the informed consent form
• Absence of current malignancies at other sites, with the exception of 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 five years and are deemed at low risk for recurrence, are eligible for the study;
• No prior history of clinically significant autoimmune disease, Crohn's disease, ulcerative colitis;
• No history of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Silgard®, Cervarix®, Gardasil®) are not excluded);
• No known or suspected hypersensitivity to component(s) of investigational product or cisplatin contraindication (e.g. peripheral neuropathy ≤ grade 2 or ototoxicity ≤ grade 2 as per CTCAE v4);
• No previous pelvic RT;
• No previous chemotherapy for this tumor;
• No patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy;
• No receipt of any immunotherapy within 4 weeks of start of protocol treatment;
• No prior major surgery within 4 weeks of randomization from which the patient has not recovered.