Ensayos clínicos

Inclusion Criteria:

• Signed written informed consent in accordance to ICH-GCP and national/local regulation before undertaking any protocol-specific procedures.
• Newly diagnosed stage III or IVA squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx excluding HPV-positive oropharynx primaries.
• Patients must have undergone gross total resection of the primary tumor.
• Patients must be eligible for adjuvant therapy.
• Tumor tissue from surgery and peripheral blood sample must be available for exome and transcriptome sequencing.
• Female or male patients, aged at least 18 years.
• Patient must have completed adjuvant therapy and have a post-treatment CT or MRI of the head and neck and CT-scan of the chest documenting CR. Imaging has to be performed 3 months after completion of adjuvant therapy and within 6 weeks prior to randomization.
•  Patients must have recovered from the toxicities of adjuvant therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate hematological, hepatic and renal functions:
  • Hemoglobin ≥ 9.0 g/dL;
  • Neutrophils count ≥ 1.5 x10^9 /L;
  • Total lymphocytes count ≥ 0.5 x10^9 /L;
  • Platelets count ≥ 100 x10^9 /L;
  • Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert’s syndrome who may be included if total bilirubin ≤ 2.5 x ULN);
  • Serum transaminases: alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 2.5 x ULN;
  • Calculated creatinine clearance ≥ 40 mL/min using the Cockroft & Gault formula;
  • 40 mL/min using the Cockroft & Gault formula;
  • Serum albumin ≥ 30 g/L.
• No locoregional relapse or occurrence of distant metastases within 6 weeks prior to randomization.
• No active infection.
• Highly Effective contraception (i.e. methods with a failure rate of less than 1% per year) during the study period and for 3 months after the last study treatment administration for female patients of childbearing potential (WOCBP) and for male patients who are sexually active with WOCBP. Highly effective contraception methods are defined as:
  • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, intrauterine devices (IUDs) such as Mirena and Nonhormonal IUDs such as ParaGard for WOCBP patient or male patient’s WOCBP partner;
  • Tubal ligation;
  • Vasectomy In addition to highly effective contraception, participating male patients must use a condom during the study period and for 3 months after the last study treatment administration.
• Negative blood pregnancy test for female patients of childbearing potential.

Exclusion Criteria:

• Less than 18 years of age.
• Patients with carcinoma of the nasopharynx, squamous cell-carcinoma of unknown primary, squamous cell carcinoma that originates from the skin and salivary gland or paranasal sinus, non-squamous histologies.
• Prior exposure to cancer immunotherapy including anti-cancer vaccines, any antibody targeting T-cell co-regulatory proteins such as anti-PD1, anti-PDL1 or anti-CTLA4 antibodies.
• Other active malignancy requiring concurrent systemic intervention.
• Patients with previous malignancies other than the target malignancy to be investigated in this trial (exceptions: non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry. Additional therapy must not be planned or required during the study period.
• Patients with any organ transplantation, including allogeneic stem cell or bone marrow transplantation.
• Any known allergy or reaction to eggs or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products.
• Known history of positive testing for Human Immunodeficiency Virus (HIV) or known Acquired Immune Deficiency Syndrome (AIDS).
• Clinical or laboratory history or evidence of Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) indicating acute or chronic infection.
• Any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 10 mIU/mL)
• Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to TG4050 treatment initiation, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
• Vaccination with a live vaccine for the prevention of infectious diseases in the four-week period prior to TG4050 treatment initiation.
• Treatment with another investigational agent within 30 days prior to TG4050 treatment initiation.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social circumstances that could limit compliance with study requirements