It is planned to study the effectiveness of low-dose immunotherapy (IT) nivolumab 40 mg for either 2 courses of therapy or 6 courses as preoperative therapy in patients with dMMR/MSI locally advanced CRC. Parallel recruitment into subgroups of patients by randomization is assumed.

For dMMR/MSI locally advanced gastric cancer, it is planned to study the effectiveness of low-dose immunotherapy nivolumab 40 mg with or without the addition of chemotherapy (CT) in the FOLFOX regimen as preoperative therapy.

Subgroup A includes 6 cycles of IV CT FOLFOX + IV administration of nivolumab 40 mg once every 14 days, subgroup B - 2 cycles of intravenous administration of nivolumab at a dose of 40 mg once every 14 days, and subgroup C - 6 cycles of intravenous administration of nivolumab at a dose of 40 mg once a day 14 days. Thus, it is planned to gradually include patients in the treatment subgroups.

The frequency of complete therapeutic tumor pathomorphoses (pCR, TRG1) will be evaluated as the primary endpoint. Secondary goals are to study the safety of drug doses, to assess the frequency of pronounced therapeutic tumor pathomorphoses (MPR, TRG 1-2), to assess disease-free survival (PFS), the frequency of R0 resections, overall survival(S), and the frequency of objective response.

To study the use of low-dose immunotherapy in combination with chemotherapy in patients with metastatic dMMR/MSI CRC and gastric cancer in the first line of therapy, it is planned to use a combination of nivolumab 40 mg with FOLFOX regimen once every 14 days for 8 treatment cycles, followed by a switch to supportive intravenous monotherapy with nivolumab 40 mg.

It is planned to study the effectiveness of low-dose immunotherapy (IT) nivolumab 40 mg for either 2 courses of therapy or 6 courses as preoperative therapy in patients with dMMR/MSI locally advanced CRC. Parallel recruitment into subgroups of patients by randomization is assumed.

For dMMR/MSI locally advanced gastric cancer, it is planned to study the effectiveness of low-dose immunotherapy nivolumab 40 mg with or without the addition of chemotherapy (CT) in the FOLFOX regimen as preoperative therapy.

Subgroup A includes 6 cycles of IV CT FOLFOX + IV administration of nivolumab 40 mg once every 14 days, subgroup B - 2 cycles of intravenous administration of nivolumab at a dose of 40 mg once every 14 days, and subgroup C - 6 cycles of intravenous administration of nivolumab at a dose of 40 mg once a day 14 days. Thus, it is planned to gradually include patients in the treatment subgroups.

The frequency of complete therapeutic tumor pathomorphoses (pCR, TRG1) will be evaluated as the primary endpoint. Secondary goals are to study the safety of drug doses, to assess the frequency of pronounced therapeutic tumor pathomorphoses (MPR, TRG 1-2), to assess disease-free survival (PFS), the frequency of R0 resections, overall survival(S), and the frequency of objective response.

To study the use of low-dose immunotherapy in combination with chemotherapy in patients with metastatic dMMR/MSI CRC and gastric cancer in the first line of therapy, it is planned to use a combination of nivolumab 40 mg with FOLFOX regimen once every 14 days for 8 treatment cycles, followed by a switch to supportive intravenous monotherapy with nivolumab 40 mg.

One-year AFD will be evaluated as the primary endpoint in the group with metastatic disease. Secondary goals are to study the safety of drug doses, and to evaluate one-year DFS, OS, and CSR.

To develop methods for personalizing low-dose IT, it is planned to compare the number of PD-1-positive cells before treatment and during immunotherapy. It is expected to detect PD-1 blockade on the lymphocyte surface during therapy and assess its duration. The results of the study will be presented in the form of an indicator of the number of PD-1-positive cells (%) and an indicator of the protein density on the surface of positive cells (MFI - average fluorescence intensity).

Peripheral venous blood samples in an anticoagulant tube (3 ml) are planned before the start of therapy, before the second injection of anti-PDL antibodies and, if long-term immunotherapy is received, after 8 weeks. Monoclonal antibodies to CD45, CD4, CD8, CD279 (PD-1), and IgG4 will be used as reagents. The equipment is a BD FACS Canto II flow cytometer.

To analyze the features of radiological evaluation of the effectiveness of checkpoint inhibitor therapy (pseudoprogression), radiological monitoring will be performed before the start of therapy, before surgical treatment, and every 8 weeks of treatment with prolonged immunotherapy. The response to treatment will be evaluated according to the RECIST criteria in revision 1.1.

Inclusion Criteria:

• Availability of voluntarily signed informed consent from the patient;
• Men and women, 18 years old \