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

Sponsor
Blokhin's Russian Cancer Research Center
Study ID
NCT07542262
Phase
PHASE2
Status
Enrolling By Invitation

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Low-dose nivolumab — DRUG
    nivolumab 40 mg
  • Low-dose nivolumab with/without chemotherapy — DRUG
    Subgroup A - 6 cycles of IV CT FOLFOX + nivolumab 40 mg once every 14 days; Subgroup B - 2 cycles of IV of nivolumab 40 mg once every 14 days; Subgroup C - 6 cycles of of nivolumab 40 mg once a day 14 days.
  • Low-dose nivolumab combined with chemotherapy — DRUG
    Metastatic dMMR/MSI CRC and gastric cancer in the first line - the use of low-dose immunotherapy in combination with chemotherapy (nivolumab 40 mg + FOLFOX regimen once every 14 days for 8 cycles + maintenance monotherapy nivolumab 40 mg)

Study Details

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.

Key Dates

Start date
Jun 3, 2025
Status verified
Apr 2026
Primary completion
Mar 30, 2028
Completion
Mar 31, 2028

Study Design

Enrollment
128 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1. dMMR/MSI locally advanced CRC
    Efficacy of low-dose immunotherapy (IT) nivolumab 40 mg for either 2 courses of therapy or 6 courses as preoperative therapy. Parallel recruitment of patients into patient subgroups by randomization.
  • Experimental: Cohort 2. dMMR/MSI locally advanced gastric cancer
    Subgroup A includes 6 cycles of IV CT FOLFOX + nivolumab 40 mg once every 14 days; subgroup B - 2 cycles of intravenous administration of nivolumab 40 mg once every 14 days; subgroup C - 6 cycles of of nivolumab 40 mg once a day 14 days. It is planned to gradually include patients in the subgroups.
  • Experimental: Cohort 3. Metastatic dMMR/MSI CRC and gastric cancer in the first line
    The use of low-dose immunotherapy in combination with chemotherapy (nivolumab 40 mg + FOLFOX regimen once every 14 days for 8 cycles + maintenance monotherapy nivolumab 40 mg)

Primary Outcome Measure

Pathological complete response (pCR) - for M0 [ Time Frame: up to 8 months ]

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