Neoadjuvant Iparomlimab/Tuvonralimab Plus CAPEOX Versus Iparomlimab/Tuvonralimab Plus CAPEOX and Propranolol for Locally Advanced pMMR Colon Cancer: A Prospective, Single-Center, Multi-Cohort Study

Starting soon · Phase 2

Conditions studied: Colon Cancer (Stage II &Amp; III), Immunotherapy, Beta Blocker, Neoadjuvant Chemoimmunotherapy

In brief

The goal of this prospective, single-center, multi-cohort clinical trial is to evaluate the efficacy and safety of neoadjuvant Iparomlimab/Tuvonralimab combined with CAPEOX, with or without propranolol, in patients with locally advanced pMMR (MSS) colon cancer. The main questions it aims to answer are: * What is the major pathological response (MPR) rate after neoadjuvant treatment and curative surgery (e.g., ≤10% viable tumor cells in the resected primary tumor)? * What are the key secondary outcomes (e.g., R0 resection rate, tumor regression grade, objective response rate, disease-free survival) and the safety/tolerability profile of these neoadjuvant regimens? If there is a comparison group: Researchers will compare Cohort A (Iparomlimab/Tuvonralimab + CAPEOX) versus Cohort B (Iparomlimab/Tuvonralimab + CAPEOX + propranolol) to see whether adding propranolol improves pathological and clinical responses while maintaining acceptable safety. Participants will: * Receive neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX for a protocol-defined number of cycles, with or without propranolol depending on cohort assignment. * Undergo curative-intent surgical resection after completing neoadjuvant therapy. * Be followed for postoperative treatment, adverse events, and longer-term outcomes (e.g., recurrence and survival), and may contribute tumor/blood samples for exploratory biomarker analyses related to treatment response.

Key facts

Study ID

NCT07549906

Run by

Sun Yat-sen University

People needed

45

Starts

2026-04-20

Expected to finish

2026-12-31

Last updated by the study team

2026-04-24

Who can join

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

You may qualify if…

• Participants must meet all of the following:
• Diagnosis / Stage: Histologically confirmed and radiologically assessed colon adenocarcinoma that is T4, or T3 with lymph node metastasis, with tumor location ≥10 cm from the anal verge, and clinical TNM staging per AJCC/UICC 8th edition.
• Measurable disease: At least one measurable lesion per RECIST v1.1 (non-lymph node lesion long axis ≥10 mm on CT; lymph node lesion short axis ≥15 mm on CT).
• pMMR/MSS confirmation: pMMR by IHC on colonoscopy biopsy (MMR proteins by immunohistochemistry), or MSS/MSS-L by PCR or NGS.
• Treatment-naïve for current colon cancer: No prior anti-tumor treatment for colon cancer. (If Lynch syndrome, no anti-tumor treatment for the current diagnosis.)
• Age: 18 to 75 years, any sex.
• Performance status / organ function: ECOG 0-1 with adequate organ and bone marrow function.
• Informed consent: Written informed consent signed before enrollment.
• Life expectancy: Expected survival >12 weeks.
• Hematology and chemistry (without blood products or growth factors within 14 days):
• Hemoglobin ≥60 g/L
• ANC ≥1.5 × 10⁹/L
• Platelets ≥75 × 10⁹/L
• Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min (Cockcroft-Gault)
• Total bilirubin ≤1.5 × ULN
• AST or ALT ≤2.5 × ULN (if abnormal due to liver metastasis, ≤5 × ULN)
• Urine protein <2+; if ≥2+, 24-hour urine protein ≤1 g
• Coagulation / bleeding-thrombosis status: No active bleeding and no thrombotic disease; patients may be eligible if thrombosis is treated and stable for ≥3 months. Must meet:
• INR ≤1.5 × ULN
• APTT ≤1.5 × ULN
• PT ≤1.5 × ULN
• Thyroid function within normal range:
• Free T4 12-22 pmol/L
• Free T3 2.8-7.1 pmol/L
• TSH 0.27-4.2 mIU/L

You may not qualify if…

• Participants meeting any of the following are excluded:
• History of allergic disease, severe drug allergy, known allergy to macromolecular protein products, or allergy to Iparomlimab/Tuvonralimab (protocol wording originally referenced the Chinese drug name).
• Cardiopulmonary insufficiency or hepatic/renal insufficiency such that CAPEOX cannot be tolerated; known allergy to oxaliplatin or capecitabine.
• Presence of distant metastasis.
• Any of the following complications:
• Major GI bleeding, perforation, or GI obstruction (including paralytic ileus)
• Symptomatic heart disease (including unstable angina, myocardial infarction, heart failure)
• Uncontrolled diabetes, hypertension, or hypotension
• Uncontrolled diarrhea that interferes with daily activities despite adequate treatment
• Use of immunosuppressants or systemic/absorbable local steroids for immunosuppression (>10 mg/day prednisone equivalent) and still using within 2 weeks before enrollment
• Poorly controlled cardiac symptoms or clinically significant heart disease, including:
• NYHA class >II heart failure
• Unstable angina
• Myocardial infarction within 1 year
• Clinically significant supraventricular or ventricular arrhythmia requiring treatment/intervention
• Prior or current thyroid dysfunction that cannot be maintained within normal range despite medication.
• Use of traditional Chinese immune modulators within 2 weeks before treatment, or receipt of systemic anti-tumor therapy (chemotherapy, immunotherapy, biologic therapy, etc.) or TCM anti-tumor therapy within 4 weeks before treatment.
• Active infection, or unexplained fever >38.5°C during screening or before first dose (tumor-related fever may be allowed per investigator judgment).
• History or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, known active pulmonary tuberculosis, severely impaired lung function, etc.
• Congenital or acquired immunodeficiency, e.g., HIV infection (HIV 1/2 antibody positive).
• Acute or chronic active HBV: HBsAg(+) or HBcAb(+) requires HBV DNA testing. Eligible only if HBV DNA <2×10³ copies/mL or <200 IU/mL or below LLOD; HBsAg(+) must receive anti-HBV therapy during study treatment; HBcAb(+)/HBsAg(-)/anti-HBs(-) with negative viral load does not require prophylaxis but requires close monitoring.
• Acute or chronic active HCV: HCV antibody positive and HCV RNA above LLOD.
• Receipt of a live vaccine within 4 weeks prior to study drug or anticipated need for live vaccination during the study.
• Known history of psychoactive substance abuse, alcoholism, or drug abuse.
• Pregnant or breastfeeding women, or men/women unwilling to use contraception.

Full record on ClinicalTrials.gov

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