Neoadjuvant Prolgolimab Monotherapy in Locally Advanced MMR-deficient Colorectal Cancer

NCT06428487 | Completed Phase 2

• 1 other identifier: 125
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase II study patients with stage II-III MSI/dMMR colorectal adenocarcinoma with no signs of distant metastases will be treated with immunotherapy (prolgolimab). The duration of treatment is 6 months (12 cycles)

Conditions

Colorectal Cancer

Keywords

colorectal cancer; immune checkpoint inhibitors; microsatellite instability

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  Absence of malignant cells on the specimen of colon/rectal resection in patients who were previously treated with neoadjuvant immunotherapy

  up to 8 months

Secondary Outcomes (7)

• Durable complete clinical response rate (DRR)

  up to 12 months

• Progression-free survival (PFS)

  12 months

• Overall survival (OS)

  12 months

• Objective response rate (ORR)

  up to 8 months

• R0 resection rate

  up to 8 months

Study Arms (1)

Prolgolimab monotherapy

EXPERIMENTAL

The patients will be treated with prolgolimab 1 mg/kg every 2 weeks during 6 months (12 cycles) until surgery

Drug: Prolgolimab

Interventions

Prolgolimab DRUG

Prolgolimab infusions 1 mg/kg

Prolgolimab monotherapy

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
• 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

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, 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

Related Publications (1)

• Kuznetsova O, Zagidullina A, Drobot N, Prokopiev A, Ivanov M, Fedyanin M, Mamedli Z, Aliev V, Polynovsky A, Dzhumabaev K, Aniskin A, Stroganova A, Karasev I, Tryakin A. Neoadjuvant Immunotherapy With Prolgolimab in Patients With Locally Advanced Microsatellite Instability/Defective Mismatch Repair Colorectal Cancer. JCO Precis Oncol. 2025 Dec;9:e2500602. doi: 10.1200/PO-25-00602. Epub 2025 Dec 10.

  PMID: 41370727 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Microsatellite Instability

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; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: May 24, 2024
• Study Start: March 31, 2022
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

RU (1)