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

NCT07542262 | Enrolling By Invitation Phase 2

• 1 other identifier: 3NIVO402025
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer; Gastric Cancer

Keywords

colorectal cancer; gastric cancer; low-dose immunotherapy; MSI; dMMR

Outcome Measures

Primary Outcomes (2)

• Pathological complete response (pCR) - for M0

  pCR: absence of malignant cells on the specimen of colon/rectal resection in patients who were previously treated with neoadjuvant immunotherapy, TRG1 by Mandard

  up to 8 months

• One-year progression-free survival (PFS) - for M1

  Time from initiation of treatment to the occurrence of disease progression or death.

  12 months

Secondary Outcomes (5)

• Major pathologic response (MPR) - for M0

  up to 8 months

• Progression-free survival (PFS) - for M0

  12 months

• R0 resection rate - for M0

  up to 8 months

• Overall survival (OS) - for M0 and M1

  12 months

• Objective response rate (ORR) - for M0 and M1

  up to 8 months

Study Arms (3)

Cohort 1. dMMR/MSI locally advanced CRC

EXPERIMENTAL

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.

Drug: Low-dose nivolumab

Cohort 2. dMMR/MSI locally advanced gastric cancer

EXPERIMENTAL

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.

Drug: Low-dose nivolumab with/without chemotherapy

Cohort 3. Metastatic dMMR/MSI CRC and gastric cancer in the first line

EXPERIMENTAL

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)

Drug: Low-dose nivolumab combined with chemotherapy

Interventions

Low-dose nivolumab DRUG

nivolumab 40 mg

Cohort 1. dMMR/MSI locally advanced CRC

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.

Cohort 2. dMMR/MSI locally advanced gastric cancer

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)

Cohort 3. Metastatic dMMR/MSI CRC and gastric cancer in the first line

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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.
• Life expectancy less than 6 months.
• The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in 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;
• 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);
• 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);

Sponsors & Collaborators

• Blokhin's Russian Cancer Research Center: lead

Study Sites (1)

N.N. Blokhin NMRCO

Moscow, Russia

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms

Interventions

Nivolumab; Drug Therapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort 1. dMMR/MSI for 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. Cohort 2. dMMR/MSI locally advanced gastric cancer - efficacy of low-dose immunotherapy nivolumab 40 mg with or without addition of chemotherapy (CT) in FOLFOX regimen as preoperative therapy. 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. 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)

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: April 21, 2026
• Study Start: June 3, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

RU (1)