Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact

Prior treatment

• The use of immunosuppressive therapy for 90 days before inclusion in the study.
• Absence of adequate venous access, allowing to perform infusion therapy.
• Use of drugs or therapies listed in the Prohibited Therapies section.
• Persons with alcohol, drug or drug addiction
• The need to use therapy during the study that is not permitted by this protocol.
• Previous serious systemic reaction or adverse effect from a previous smallpox vaccination.

Other illness

• Severe cardiovascular diseases in the past and at the present time (myocardial infarction, hypertension, stroke, phlebothrombosis, coronary insufficiency requiring medical correction, etc.).
• Allergic reactions to any pharmacological drugs.
• Positive reaction of serological study to HIV, hepatitis B and C, syphilis.
• Myeloproliferative disorders requiring systemic therapy, according to anamnesis.
• Exfoliative skin diseases (e.g. eczema or atopic dermatitis) requiring systemic therapy, according to anamnesis.
• Mental illness that prevents the patient from understanding the treatment plan.

Lab values

• Clinically significant renal pathology (bilateral renal artery stenosis, renal artery stenosis in a single kidney, patients undergoing kidney transplantation, clinically significant decrease in sodium, hypo- or hyperglycemia, creatinine exceeding the upper limit of normal values more than 2 times).
• Any clinical condition or deviation from normal laboratory and vital signs at screening that, in the opinion of the Investigator, would preclude the safe completion of the study protocol.

Other

• Incompatibility of patients with the inclusion criteria mentioned above.
• Impaired renal function (decreased glomerular filtration rate less than 40 ml / min / 1,73 m2, estimated by the CKD-EPI calculation method).
• The inability of the CT.
• The need for any vaccination/revaccination during the study.
• Pregnancy or breastfeeding, refusal of a reliable method of contraception.
• Participation in other clinical trials currently or within the last 3 months.

• Female patients with recurrent and/or metastatic breast cancer, for whom the standard methods of treatment are considered ineffective by the medical commission.
• Histologically confirmed progressive / metastatic tumor.
• Detectable and measurable tumor foci - at least one measurable tumor site measured by CT (with a diameter more than 1 cm) and at least one tumor site for biopsy.
• Body weight index from 18.5 to 30 kg / m2 with body weight from 55 to 100 kg inclusive.
• Before inclusion of patients in the study, at least one of the following types of therapy was previously performed:
  • 5.1 previous radiation therapy completed more than 4 weeks ago before the screening visit; 5.2 previous immunotherapy completed more than 4 weeks ago before the screening visit; 5.3 previous hormone therapy completed more than 4 weeks ago before the screening visit; 5.4 previous chemotherapy completed more than 4 months ago before the screening visit.
• The indicator of general status is not more than 2 points according the WHO scale.
• Age - 18 years or older.
• The level of ALT and AST does not exceed the upper limits of normal values more than 4 times.
• Hematological parameters: the number of leukocytes \> 3000/µl, platelets \> 100000/µl, hemoglobin \> 8 g/DL.
• Negative result of the PCR test for the presence of SARS-CoV-2 virus RNA on screening.
• No signs of SARS at least 14 days before screening.
• Patients, 12.1. Not vaccinated against the SARS-CoV-2 coronavirus. OR 12.2. Vaccinated/revaccinated against SARS-CoV-2 coronavirus more than 90 days before the screening visit.
• Patient's ability to perform the study procedure and provide written informed consent in accordance with the GCP and local laws.