The Efficacy and Safety of Neoadjuvant Therapy With Iparomlimab and Tuvonralimab in Locally Advanced MSI-H/dMMR Colorectal Cancer: An Prospective, Single-Arm Study (Neo-IT)

Not Applicable

Active, not recruiting

• Conditions: dMMR/MSI-H-type Rectal Adenocarcinoma
• Interventions: Drug: Ipalolimab and Tovorilimab

• Registration Number: NCT07160647
• Lead Sponsor: Sir Run Run Shaw Hospital

Brief Summary

Immunotherapy may bring revolutionary changes to the preoperative neoadjuvant treatment mode for dMMR/MSI-H locally advanced rectal cancer. According to the existing theory, the use of Iparomlimab and Tuvonralimab may be the best solution. In this study, the investigators will perform single-cell sequencing of participants tissue samples, fully explore the multi-dimensional omics information of tumors and microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study Start: 2025-08-20
• Study First Submitted: 2025-08-25
• Study First Submitted QC: 2025-08-29
• Last Update Submitted: 2025-08-29
• Study First Posted: 2025-09-08
• Last Update Posted: 2025-09-08
• Primary Completion: 2027-08-30
• Study Completion: 2030-08-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Patients willing to receive neoadjuvant therapy.

2. Age ≥18 years.

3. Histologically confirmed primary colorectal adenocarcinoma (without squamous or sarcomatoid components).

4. Radiologically assessed (contrast-enhanced CT or MRI) as surgically resectable stage IIB-III (limited to cT4 or cN+ per AJCC 8th edition).

5. Confirmed dMMR or MSI-H status by immunohistochemistry or MSI genetic testing.

6. Lesions diagnosed by investigators as amenable to radical resection (R0 resection) without requiring multi-organ resection prior to neoadjuvant therapy.

7. Voluntary participation with signed informed consent.

8. ECOG performance status score of 0-1.

9. No prior antitumor or immunotherapy before enrollment.

10. Adequate organ and bone marrow function defined as:

    1. Hematology: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L; Platelets (PLT) ≥100×10⁹/L; Hemoglobin (HGB) ≥7.0 g/dL.
    2. Liver function: Total Bilirubin (TBIL) ≤1.5×ULN; Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) ≤3×ULN; Serum Albumin (ALB) ≥28 g/L.
    3. Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; Urine dipstick shows protein <2+; for subjects with baseline urine dipstick protein ≥2+, a 24-hour urine collection must demonstrate protein <1 g.
    4. Coagulation: International Normalized Ratio (INR) ≤1.5 and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN.

11. No severe comorbidities jeopardizing survival (life expectancy <5 years).

12. Fertile female subjects or male subjects with fertile partners must use effective contraception during and for 6 months after treatment. Postmenopausal status or negative urine/serum pregnancy test for premenopausal females.

Exclusion Criteria

• 1.Prior antitumor therapy for the disease under investigation, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.

  2.Previous treatment with anti-PD-1, anti-PD-L1, anti-programmed death ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agents, or any other drugs targeting T-cell co-stimulation or immune checkpoint pathways (e.g., OX40, CD137), as well as adoptive cell immunotherapy.

  3.Concurrent participation in another interventional clinical study. 4.Treatment with any investigational drug or device within 4 weeks prior to the first dose of the study drug.

  5.Within 7 days before screening laboratory tests: receipt of blood transfusion, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), or IL-11 therapy.

  6.Use of immunosuppressive drugs within 4 weeks before the first dose of the study drug, excluding: intranasal/inhaled topical steroids or local steroid injections (e.g., intra-articular); systemic corticosteroids at doses ≤10 mg/day prednisone or equivalent; corticosteroids as premedication for allergic reactions (e.g., CT scan premedication).

  7.Use of Chinese herbal medicine with antitumor indications or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 1 week before the first dose of the study drug.

  8.Receipt of live or attenuated vaccines within 4 weeks before the first dose or anticipated during the study.

  9.Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose, anticipated need for major surgery during the study (except protocol-defined radical resection for colon cancer), or presence of unhealed wounds, ulcers, or fractures.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
a combined treatment regimen of immunotherapy and radical surgical resection	Ipalolimab and Tovorilimab	Eligible patients with advanced MSI-H/dMMR colorectal cancer will receive a combined treatment regimen of immunotherapy and radical surgical resection. The specific procedures are as follows: Anti-PD-1/CTLA-4 dual immunotherapy (5 mg/kg, IV, D1, Q3W, 4 cycles). Radical surgical resection will be performed after the completion of immunotherapy.

Primary Outcome Measures

Name	Time	Method
The primary objective of the study is to evaluate the pathologic complete response (pCR) rate	Up to 13 weeks (once surgery is done)	Description: pCR was defined as the absence of viable tumour cells in the resected primary tumour specimen and all sampled regional lymph nodes (ypT0N0).

Secondary Outcome Measures

Name	Time	Method
Tumor regression grade	Up to 13 weeks (once surgery is done)	Tumor Regression Grade（TRG）will be done via pathologic assessment on the surgical specimen with AJCC/CAP TRG system
The proportion of participants who remain progression free at 3 years	Up to 3 years	Defined as the percentage of patients without disease recurrence or progression after 3-year follow-up
The proportion of participants who remain survival at 3 years	Up to 3 years	Defined as the percentage of patients alive after 3-year follow-up
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0	Up to 3 years	Treatment- related adverse events are assessed by NCI-CTCAE v5.0 in each visit
Quality of life of the patients	up to 3 years	Quality of life is measured via FACT-C questionnaire in each visit.

Trial Locations

Locations (1)

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine,; 🇨🇳 Hangzhou, Zhejiang, China