Neoadjuvant Low-dose Immunotherapy in Locally Advanced MMR-deficient Colorectal Cancer (NIVO1002024)

Phase II Open-label Non-randomized Study of Neoadjuvant Low-dose Immunotherapy in Patients With Locally Advanced Colorectal Cancer With Microsatellite Instability (MSI)/Mismatch Repair Deficiency (dMMR)

Patients with clinical stage II-III dMMR/MSI colorectal adenocarcinoma will be treated with low-dose immunotherapy: nivolumab 100 mg or pembrolizumab 100 mg. The duration of treatment is 6 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer (CRC); Colorectal Cancer (MSI-H)
• Intervention / Treatment: Drug: Nivolumab; Drug: Pembrolizumab

Detailed Description

Patients with clinical high risk stage II (T3 with extramural extension ≥ 5mm or T4), stage III dMMR/MSI CRC will be treated with low-dose immunotherapy: nivolumab 100 mg every 2 weeks or pembrolizumab 100 mg every 4 weeks, then will be underwent surgery after 6 months of immunotherapy. Pts who refuse surgery and/or in case of complete clinical response (cCR) will continue therapy up to 1 year.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russia
  • Moscow, Russia
    • N.N. Blokhin NMRCO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Availability of voluntarily signed informed consent from the patient
• Histologically confirmed adenocarcinoma of the colon or rectum;
• 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;
• Presence of MSI/dMMR in the tumor;
• ECOG 0-2;
• No contraindications to surgical treatment of malignancy

Exclusion Criteria:

• Previous therapy with the inclusion of monoclonal antibodies - anti-PD1, anti-PD-L1, anti PD-L2, anti-CTLA4 antibodies and other immunotherapy drugs
• 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
• 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, 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);
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; The patients will be treated with nivolumab 100 mg every 2 weeks during 6 months until surgery	Drug: Nivolumab; Nivolumab 100 mg infusion
Experimental: Pembrolizumab; The patients will be treated with pembrolizumab 100 mg every 4 weeks during 6 months until surgery	Drug: Pembrolizumab; Pembrolizumab 100 mg infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (pathological complete response - pCR + durable clinical complete response - cCR)	pCR: absence of malignant cells on the specimen of colon/rectal resection in patients who were previously treated with neoadjuvant immunotherapy cCR: absence of detectable tumor via endoscopy and MRI up to 6 months	up to 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Time from initiation of treatment to the occurrence of disease progression or death.	12 months
Overall survival (OS)	Time from initiation of treatment to death.	12 months
Objective response rate (ORR)	percentage of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more)	up to 8 months
Major pathologic response (MPR)	Rate of pathologic response TRG 1-2	up to 8 months
Incidence of Treatment-Related Adverse Events as assessed by investigator	Incidence of Adverse Events assessed according to CTCAE version 5	up to 6 months
Durable complete clinical response rate (DRR)	A continuous response [complete or partial objective response] beginning within 6 months of treatment and lasting ≥6 months	up to 12 months

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2024
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer; immune checkpoint inhibitors; MSI; dMMR; low-dose immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; pembrolizumab
• Other Study ID Numbers: 3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No