SCRT Combined With Chemotherapy and Iparomlimab and Tuvonralimab in MSS or pMMR Patients With Locally Advanced Rectal Cancer

Recruiting now · Phase 2

Conditions studied: Locally Advanced Rectal Cancer (LARC)

In brief

Colorectal cancer ranks as the third most prevalent malignancy worldwide and the second leading cause of cancer-related mortality. For patients with locally advanced rectal cancer (LARC) classified as T3-4/N+ without distant metastasis, achieving organ preservation and functional integrity while pursuing curative treatment remains a formidable clinical challenge. This study aims to evaluate the efficacy and organ preservation rates of a novel neoadjuvant regimen comprising short-course radiotherapy followed by four cycles of CAPEOX combined with Iparomlimab and Tuvonralimab in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) LARC. Furthermore, the project will investigate potential predictive biomarkers for complete response (CR) within this immunotherapy-based total neoadjuvant therapy (iTNT) paradigm.

Key facts

Study ID

NCT06864013

Run by

First Affiliated Hospital of Zhejiang University

People needed

116

Starts

2025-01-06

Expected to finish

2029-12-31

Last updated by the study team

2026-01-14

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Sign a written Informed Consent Form (ICF) and be able to comply with the visits and related procedures stipulated in the protocol
• Age between 18 and 75 years old
• Histologically confirmed rectal adenocarcinoma
• According to the AJCC 8th Edition staging, imaging evaluation (enhanced CT or enhanced MRI) confirms resectable locally advanced rectal cancer (AJCC 8th Edition staging cT3-4 / cN+)
• Patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) rectal cancer
• At least one evaluable lesion according to RECIST v1.1 criteria
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1
• Adequate organ and bone marrow function, defined as follows:
• Blood count: Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L; Platelet (PLT) ≥100×10\^9/L; Hemoglobin (HGB) ≥10.0 g/dL.
• Liver function: Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal (ULN); Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤3×ULN. Serum albumin (ALB) ≥35 g/L.
• Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 ml/min (calculated using the Cockcroft-Gault formula or standard 24-hour urine collection method); Urine dipstick test shows urine protein <2+; For subjects with baseline urine dipstick test showing urine protein ≥2+, a 24-hour urine collection should be performed, and the protein content in the 24-hour urine should be <1 g.
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN. Certain anticoagulant drugs (such as antiplatelet drugs, vitamin K antagonists, etc.) need to be discontinued 7\~14 days before surgery and replaced with other drugs (such as low molecular weight heparin)
• No serious concomitant diseases that threaten the subject's survival (resulting in an expected survival time of less than 5 years)
• Female subjects of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 6 months after the treatment period. Female subjects must have evidence of postmenopausal status or a negative urine or serum pregnancy test result for premenopausal female subjects.

You may not qualify if…

• Patients with rectal cancer who have been tested for microsatellite instability as MSI-H or mismatch repair as dMMR
• Patients who have previously received any anti-tumor treatment for the studied disease, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc. This includes previous treatment with anti-PD-1, anti-PD-L1, anti-programmed death receptor ligand 2 (PD-L2) or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) drugs, or any other drugs acting on T cell co-stimulation or immune checkpoint pathways (such as OX40, CD137, etc.), as well as adoptive cell immunotherapy
• Simultaneous participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study
• Treatment with any investigational drug or device within 4 weeks prior to the first dose of the study drug
• History of blood transfusion within 14 days before the screening laboratory tests, or use of Granulocyte-colony stimulating factor (G-CSF), Granulocyte-Macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), or IL-11
• Use of immunosuppressive drugs within 4 weeks prior to the first dose of the study drug, excluding: intranasal inhaled local steroid therapy or local steroid injections (such as intra-articular injections); systemic corticosteroid therapy not exceeding 10 mg/day of prednisone or its equivalent physiological dose; glucocorticoids as preventive medication for allergic reactions (such as pre-CT medication); use of Chinese herbal medicine or immunomodulatory drugs with anti-tumor indications (including thymosin, interferon, interleukin, etc.) within 1 week prior to the first dose of the study drug
• Receipt of live or attenuated live vaccines within 4 weeks prior to the first dose of the study drug or expected during the study period
• Major surgical procedures (such as craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of the study drug, anticipated need for major surgery during the study treatment period (except for radical rectal cancer surgery as specified in the protocol), or presence of unhealed wounds, ulcers, or fractures
• Known active or suspected autoimmune disease or history of autoimmune disease within the past 2 years (subjects with eczema, vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in the past 2 years, history of hypothyroidism requiring only thyroid hormone replacement therapy or autoimmune hypothyroidism, and type I diabetes requiring only insulin replacement therapy may be enrolled)
• Known history of primary immunodeficiency
• Active tuberculosis, currently receiving anti-tuberculosis treatment or having received anti-tuberculosis treatment within 1 year prior to the first dose of the study drug
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Known allergy to capecitabine, oxaliplatin, anti-PD-1 monoclonal antibody, anti-CTLA-1 monoclonal antibody, anti-PD-1/CTLA-4 antibody preparation, or other monoclonal antibody components
• Ascites and pleural effusion requiring clinical intervention in the short term, symptomatic or requiring drainage of pericardial effusion
• Human immunodeficiency virus (HIV) infection (HIV antibody positive)
• Acute or chronic active hepatitis B (defined as HBsAg or only HBcAb positive and HBV DNA ≥2000 IU/mL or ≥1×10\^4 copies/mL), acute or chronic active hepatitis C (defined as HCV antibody positive and HCV-RNA level above the lower limit of detection)
• HBV DNA ≥2000 IU/mL or ≥1×10\^4 copies/mL), acute or chronic active hepatitis C (defined as HCV antibody positive and HCV-RNA level above the lower limit of detection)
• Active syphilis infection requiring treatment
• Severe infection occurring within 4 weeks prior to the first dose of the study drug or during the active phase or poorly controlled, including but not limited to hospitalization for infection, bacteremia, or complications of severe pneumonia, therapeutic oral or intravenous antibiotics within two weeks prior to the first dose
• Symptomatic congestive heart failure (New York Heart Association class II\~IV) or left ventricular ejection fraction (LVEF) <50% on echocardiography; symptomatic or poorly controlled arrhythmia; history of congenital long QT syndrome or corrected QTc >500 ms at screening (calculated using Fridericia's method)
• Uncontrolled arterial hypertension despite standard treatment (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg), history of hypertensive crisis or hypertensive encephalopathy
• Severe bleeding tendency or coagulation dysfunction, or undergoing thrombolytic therapy
• Any arterial thromboembolic event within 6 months prior to the first dose of the study drug, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack
• Esophageal or gastric varices requiring immediate intervention (e.g., ligation or sclerotherapy) or considered at high risk of bleeding by the investigator or after consultation with a gastroenterologist or hepatologist, evidence of portal hypertension (including splenomegaly on imaging) or history of variceal bleeding, subjects must undergo endoscopic evaluation within 3 months prior to enrollment
• History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of the study drug

Where it is running

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (enrolling)

Full record on ClinicalTrials.gov

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