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.
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.)
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.
Major GI bleeding, perforation, or GI obstruction (including paralytic ileus)