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)
Parallel
Iparomlimab/Tuvonralimab
DrugIparomlimab/Tuvonralimab will be administered 5 mg/kg intravenously on Day 1 of each 3-week cycle.
Capecitabine
DrugCapecitabine 1,000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle.
Oxaliplatin
Drugoxaliplatin 130 mg/m² IV on Day 1 of each 3-week cycle.
Propranolol
Drugpropranolol 10 mg orally three times daily (TID) will be given on Days 1-14 of each 3-week cycle
Major Pathological Response (MPR)
MPR is defined as ≤10% viable (residual) tumor cells in the primary tumor after completion of neoadjuvant systemic therapy and curative-intent surgery (pathology-based assessment).
R0 Resection Rate
Proportion of participants achieving complete tumor resection with microscopically negative margins (no residual tumor at the resection margin) (R0).
Tumor Regression Grade (TRG)
Pathologic tumor regression graded per NCCN TRG criteria (TRG0-TRG3) based on residual tumor and fibrosis patterns in the resected specimen.
Objective Response Rate (ORR)
Proportion of participants achieving complete response (CR) or partial response (PR) based on tumor size reduction meeting predefined criteria (RECIST v1.1). Responses (CR/PR) require confirmation by repeat imaging ≥4 weeks later.
3-year Disease-Free Survival (3y DFS)
Proportion of participants who are alive without recurrence or metastasis within 3 years after surgery.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
