Ensayos clínicos

Inclusion Criteria: 

Screening Period

• Signed written informed consent in accordance to ICH-GCP and national/local regulation before any protocol-related procedures that are not part of normal patient care.
• Female patients ≥ 18 years of age.
• Histologically confirmed high grade, stage IIIC or stage IV (FIGO staging) serous ovarian, fallopian or primary peritoneal carcinoma with abnormal CA-125 at diagnosis.
• Patients who have undergone primary debulking surgery or interval debulking surgery and completed a total of at least 5 cycles of taxane-platinum combination.
  • Note: patients may have received concurrent or maintenance bevacizumab or a PARP inhibitor.
• Patients must have achieved a complete response to therapy, as demonstrated by no residual disease on most recent CT scan and normal CA-125 not increasing by both the following: > 25% from nadir AND ≥ 10 UI/mL from nadir.
• Patient who remains disease free at least 6 months from last prior dose of cytotoxic chemotherapy (maintenance therapy with bevacizumab or a PARP inhibitor is allowed).
• Available tumor tissue, banked from previous abdominal debulking surgery and/or from a core needle biopsy performed at diagnosis if the patient received neoadjuvant chemotherapy, and peripheral blood samples for exome and transcriptome sequencing.

Treatment Period

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at treatment period initiation.
• Patients who have developed an asymptomatic relapse as defined by:
  • Cohort A: CA-125 ≥ 2 times ULN on 2 occasions at least 1 week apart (GCIG criteria) or low volume radiological disease and CA-125 > ULN. Low volume radiological disease is defined as radiologically visible disease excluding intra-hepatic or splenic metastases, ascites or pleural effusion thought to require drainage;
  • Cohort B: patient asymptomatic with measurable disease, excluding intra-hepatic or splenic metastases, ascites or pleural effusion thought to require drainage, whatever serum CA-125 level and for whom further treatment is not planned within 2 months.
  • Longest diameter on CT-scan must not exceed 2 cm for non-nodal lesions and 2.5 cm in short axis for nodal lesions.
• Adequate hematological, hepatic and renal functions:
  • Hemoglobin ≥ 9.0 g/dL;
  • Neutrophils count ≥ 1.5 x10^9 /L;
  • Lymphocytes count ≥ 0.9 x10^9 /L;
  • Platelets count ≥ 100 x10^9 /L;
  • Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert’s syndrome);
  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN;
  • Calculated creatinine clearance ≤ 45 mL/min using the Cockroft & Gault formula or ≥ 45 mL/min/1.73m² using other methods.
• Patients who received standard maintenance therapy will stop before initiation of TG4050 administration. A free-interval of at least 30 days will be respected before first dosing of TG4050 except for PARP inhibitor (at least 14 days).

Exclusion Criteria: 

Screening Period

• Patient having received any cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins such as anti-PD1, anti-PDL1 or anti-CTLA-4.
• Patients with other active malignancy ≤ 3 years prior to registration except non-melanoma skin cancer, stage 0 in situ carcinoma and recent early stage papillary thyroid cancer. If there is an history of prior malignancy, patient must not be receiving other specific treatment for their cancer.
• Patient post-organ transplantation, including allogeneic stem cell or bone marrow transplantation. History of blood transfusion within 3 weeks prior to study entry visit.
• Known history of positive testing for Human Immunodeficiency Virus (HIV) or known AIDS (Acquired Immune Deficiency Syndrome).
• Any known allergy or reaction to eggs or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products.
• Positive serology for Hepatis C Virus (HCV) or positive serum Hepatitis B surface antigen (HBsAg) within 3 months prior to or at study entry (tests required).

Treatment Period

• Measurable disease associated with the appearance of symptoms justifying initiation of further treatment.
• Major surgery within 4 weeks prior to treatment start.
• Treatment with another investigational agent within 30 days prior to TG4050 treatment initiation.
• 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 planned date, 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 for the prevention of infectious diseases with a live vaccine during the four-week period prior to TG4050 treatment initiation planned date. Furthermore, patients should not receive any live vaccine during the period of study treatment administration.
• Patient with any underlying medical condition, that in the opinion of the investigator, could make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety or toxicity of the study treatment.
• 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.
• History of myocardial infarction ≤ 6 months.

Eligibility last updated 4/20/22. Questions regarding updates should be directed to the study team contact.