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

NCT07549906 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025-FXY-242
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Colon Cancer (Stage II &Amp; III); Immunotherapy; Beta Blocker; Neoadjuvant Chemoimmunotherapy

Keywords

Colon Cancer; Neoadjuvant chemoimmunotherapy; Iparomlimab/Tuvonralimab; propranolol; CAPEOX

Outcome Measures

Primary Outcomes (1)

• 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).

  At surgery following completion of 4 cycles of neoadjuvant treatment (each cycle is 21 days); surgery is planned within 6 weeks after the last dose of neoadjuvant therapy.

Secondary Outcomes (5)

• R0 Resection Rate

  At surgery / postoperative pathology assessment (resection margin evaluation).

• Tumor Regression Grade (TRG)

  At surgery / on the resection specimen (postoperative pathology).

• Objective Response Rate (ORR)

  Up to approximately 12 weeks from treatment initiation (corresponding to 4 cycles of neoadjuvant therapy, each cycle is 21 days), assessed at pre-surgery evaluation.

• 3-year Disease-Free Survival (3y DFS)

  Up to 3 years postoperatively.

• Safety (Neoadjuvant, Perioperative, and Follow-up Periods)

  From the start of treatment up to 90 days after the last dose of study treatment (each cycle is 21 days).

Study Arms (2)

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX

EXPERIMENTAL

Participants will receive neoadjuvant Iparomlimab/Tuvonralimab in combination with CAPEOX for 4 cycles (Q3W). Iparomlimab/Tuvonralimab will be administered 5 mg/kg intravenously on Day 1 of each 3-week cycle. CAPEOX consists of oxaliplatin 130 mg/m² IV on Day 1 plus capecitabine 1,000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. Tumor assessments will be performed per protocol during neoadjuvant treatment. Curative-intent surgery will be planned after completion of neoadjuvant therapy. Postoperative adjuvant treatment will be provided at the investigator's discretion according to standard clinical practice and pathological findings.

Drug: Iparomlimab/Tuvonralimab; Drug: Capecitabine; Drug: Oxaliplatin

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + Propranolol

EXPERIMENTAL

Participants will receive neoadjuvant Iparomlimab/Tuvonralimab in combination with CAPEOX plus propranolol for 4 cycles (Q3W). Iparomlimab/Tuvonralimab will be administered 5 mg/kg intravenously on Day 1 of each 3-week cycle. CAPEOX consists of oxaliplatin 130 mg/m² IV on Day 1 plus capecitabine 1,000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle. In addition, propranolol 10 mg orally three times daily (TID) will be given on Days 1-14 of each 3-week cycle. Tumor assessments will be performed per protocol during neoadjuvant treatment. Curative-intent surgery will be planned after completion of neoadjuvant therapy. Postoperative adjuvant treatment will be provided at the investigator's discretion according to standard clinical practice and pathological findings.

Drug: Iparomlimab/Tuvonralimab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Propranolol

Interventions

Iparomlimab/Tuvonralimab DRUG

Iparomlimab/Tuvonralimab will be administered 5 mg/kg intravenously on Day 1 of each 3-week cycle.

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX; Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + Propranolol

Capecitabine DRUG

Capecitabine 1,000 mg/m² orally twice daily on Days 1-14 of each 3-week cycle.

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX; Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + Propranolol

Oxaliplatin DRUG

oxaliplatin 130 mg/m² IV on Day 1 of each 3-week cycle.

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX; Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + Propranolol

Propranolol DRUG

propranolol 10 mg orally three times daily (TID) will be given on Days 1-14 of each 3-week cycle

Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + Propranolol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Capecitabine; Oxaliplatin; Propranolol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Central Study Contacts

Rongxin Zhang, MD, PhD

CONTACT

+86 020 87343920; zhangrx@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director, Department of Colorectal Surgery, Chief Surgeon.

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: April 24, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04