Low-dose Immunotherapy in Metastatic and Locally Advanced Colorectal and Gastric MSI/dMMR Cancers

Ki vehet részt

• Availability of voluntarily signed informed consent from the patient
• Men and women, 18 years old </=
• Histologically confirmed adenocarcinoma of the colon/rectum/stomach
• Presence of MSI/dMMR in the tumor
• For M0-cohort: locally advanced tumor - cT3-4N0-2M0 according to CT for tumors of the colon and sigmoid colon; cT3 with a depth of tissue invasion ≥5mm (cT2N0 and higher for lower ampullary cancer) or T4 or involvement of the lateral resection margins according to MRI for rectal cancer; for gastric cancer: cT2</=, N0-3, no presence of tumour cells in peritoneum (cyt-)
• For M1-cohort: non-resectable locally-advanced, metastatic disease
• ECOG 0-2
• No contraindications to surgical treatment of malignancy

Ki nem vehet részt

• Previous therapy with the inclusion of monoclonal antibodies - anti-PD1, anti-PD-L1, anti PD-L2, anti-CTLA4 antibodies and other immunotherapy drugs
• Pregnant and lactating women, as well as planning pregnancy during the period of therapy in a clinical trial and 6 months after the end of therapy
• Patients with preserved reproductive potential who refuse to use adequate methods of contraception throughout the study and 6 months after the end of therapy or who agree to abstain from heterosexual contact
• Previous systemic therapy with immunosuppressive drugs (including, but not limited to: prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and TNF [tumor necrosis factor] antagonists) within 4 weeks before signing the informed consent form, or the need to use immunosuppressive therapy in during the first year of the study
• Complicated course of the primary tumor, requiring urgent surgical intervention
• Previously performed radiation or chemotherapy for colorectal cancer or gastric cancer, with the exception of cases of metachronous tumors over 5 years ago
• Vaccination with live vaccines within 28 days before randomization
• Participation in other interventional clinical trials less than 30 days before randomization (except in cases of dropout before the introduction of study therapy) and while participating in an ongoing clinical trial
• Significant adverse events from previous therapy, with the exception of chronic and/or irreversible events that cannot influence the assessment of the safety of the study therapy (for example, alopecia)
• The presence of any other malignant tumor, with the exception of radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years before inclusion in the study
• Active, known or suspected autoimmune diseases (patients with type 1 diabetes mellitus and hypothyroidism requiring only hormone replacement therapy, as well as autoimmune diseases with only skin manifestations [for example, vitiligo, alopecia or psoriasis without symptoms of psoriatic arthritis] are allowed to participate), that do not require systemic therapy)
• Patients with HIV infection, active hepatitis B, active hepatitis C
• The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study
• Persistence, progression or recurrence of the underlying disease or the presence of distant metastases
• Conditions limiting the patient's ability to comply with the requirements of the protocol (in the opinion of the investigator)
• Hypersensitivity or allergic reactions to the administration of drugs manufactured using Chinese hamster ovary cells, severe allergic reactions, anaphylaxis or other hypersensitivity reactions to chimeric or humanized antibodies, or any of the components of the study drug
• The use of systemic glucocorticosteroids (GCS) in replacement doses (for example, in a dose equivalent to 10 mg of prednisolone per day or less), short-term use of systemic GCS (≤7 days), inhaled and topical GCS are allowed
• Life expectancy less than 6 months