Treatment of locally advanced colorectal cancer with prolgolimab

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

This study is testing if a new immune therapy called prolgolimab can help people with locally advanced colorectal cancer feel better before their surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Blokhin's Russian Cancer Research Center (Academic / other)
• Drugs / interventions: prolgolimab, chemotherapy, immunotherapy, radiation, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Moscow)
• Trial ID: NCT06428487 on ClinicalTrials.gov

What this trial studies

This phase II open-label study aims to evaluate the efficacy of prolgolimab, an anti-PD1 immune checkpoint inhibitor, in patients with stage II-III microsatellite instability (MSI) or mismatch repair deficient (dMMR) colorectal adenocarcinoma. A total of 30 patients will receive prolgolimab at a dosage of 1 mg/kg every two weeks for six months prior to surgical intervention. The study focuses on patients with locally advanced tumors who have no signs of distant metastases, assessing the potential of immunotherapy in this specific cancer population.

Who should consider this trial

Good fit: Ideal candidates include individuals with stage II-III MSI/dMMR colorectal adenocarcinoma who are eligible for surgical treatment.

Not a fit: Patients with prior treatment involving immune checkpoint inhibitors or those with other malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve surgical outcomes and overall survival rates for patients with locally advanced MSI/dMMR colorectal cancer.

How similar studies have performed: Other studies have shown promising results with immune checkpoint inhibitors in similar patient populations, indicating a potential for success in this approach.

Eligibility criteria

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, prolgolimab or any of the components of the study drug.

Where this trial is running

Moscow

• N.N. Blokhin NMRCO — Moscow, Russian Federation (Recruiting)

Study contacts

• Study coordinator: Olesya Kuznetsova

Conditions Colorectal Cancer; colorectal cancer; immune checkpoint inhibitors; microsatellite instability