AzTrials
AzTrials

Colon Cancer (Stage II &Amp; III)Phase 2NCT07549906

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

A Phase 2 study testing Iparomlimab/Tuvonralimab, Capecitabine and Oxaliplatin in people with Colon Cancer (Stage II &Amp; III) and Immunotherapy, run by Sun Yat-sen University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Iparomlimab/Tuvonralimab, Capecitabine and Oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
No sites listed yet
Study dates
20 Apr 2026to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 28Show fewer
  • 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
  • Blood pressure requirement (screening): Average seated BP 100-150 / 60-90 mmHg, and 24-hour ambulatory BP below the threshold for Grade I hypertension.
  • Contraception / pregnancy test (for women of childbearing potential): Must use medically approved contraception during treatment and for 3 months after; pregnancy test (serum or urine HCG negative within 7 days prior to enrollment); not breastfeeding.
  • Compliance: Willing and able to comply with study procedures and safety/survival follow-up.

Who cannot join

  • 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)
Show all 30Show fewer
  • 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.
  • History of allergy to β-blockers.
  • Asthma, COPD, or other respiratory disease requiring bronchodilator therapy.
  • Definite history of hypertension (without antihypertensives: non-same-day 3 measurements with SBP ≥140 mmHg and/or DBP ≥100 mmHg, or currently receiving antihypertensive therapy).
  • Clear history of hypotension; baseline SBP <90 mmHg or DBP <60 mmHg.
  • Any other condition judged by the investigator to warrant exclusion (e.g., factors that may force early termination of study participation).

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Rongxin Zhang, MD, PhD contact

+86 020 87343920

zhangrx@sysucc.org.cn

About this study

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.
Read more

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.
Read the detailed description

This prospective, single-center, multi-cohort study evaluates a neoadjuvant treatment strategy for patients with locally advanced pMMR/MSS colon cancer, a population known to have limited sensitivity to immune checkpoint blockade alone.

The study investigates whether combining dual immune checkpoint inhibition (PD-1 and CTLA-4 blockade using Iparomlimab and Tuvonralimab) with standard chemotherapy (CAPEOX) can enhance treatment response. In addition, the study explores whether modulation of the tumor microenvironment through β-adrenergic blockade (propranolol) may further improve antitumor immune activity.

Eligible participants will be assigned to one of two treatment cohorts:

Cohort A: Neoadjuvant Iparomlimab/Tuvonralimab combined with CAPEOX Cohort B: Neoadjuvant Iparomlimab/Tuvonralimab combined with CAPEOX plus propranolol All participants will receive four cycles of neoadjuvant therapy administered every three weeks. Immunotherapy is delivered intravenously on Day 1 of each cycle, while CAPEOX is administered according to standard dosing schedules. In Cohort B, propranolol is administered orally during the chemotherapy period of each cycle.

Following completion of neoadjuvant treatment, patients will undergo curative-intent surgical resection within a protocol-defined time window. Postoperative management, including adjuvant therapy, will be determined by the treating investigator according to clinical judgment and standard practice.

Tumor response will be assessed during treatment and prior to surgery using radiographic imaging. Pathologic response will be evaluated on surgical specimens to determine treatment efficacy.

In addition to clinical outcomes, this study includes exploratory translational research components. Tumor tissue and blood samples will be collected to investigate immune-related biomarkers and molecular features associated with treatment response. These analyses include RNA sequencing, immunohistochemistry, and flow cytometry-based immune profiling.

The study uses a staged design with early stopping rules based on pathologic response, allowing for preliminary assessment of treatment activity before full cohort expansion.

Being tested
Iparomlimab/Tuvonralimab, Capecitabine, Oxaliplatin, Propranolol
Keywords
Colon Cancer, Neoadjuvant chemoimmunotherapy, Iparomlimab/Tuvonralimab, propranolol, CAPEOX
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iparomlimab/TuvonralimabDrug

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

  • CapecitabineDrug

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

  • OxaliplatinDrug

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

  • PropranololDrug

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

Study groups in NCT07549906
Study groupRoleWhat they receive
Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOXExperimentalParticipants 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.
Receives: Drug: Iparomlimab/Tuvonralimab; Drug: Capecitabine; Drug: Oxaliplatin
Neoadjuvant Iparomlimab/Tuvonralimab + CAPEOX + PropranololExperimentalParticipants 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.
Receives: Drug: Iparomlimab/Tuvonralimab; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Propranolol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. R0 Resection Rate

    Proportion of participants achieving complete tumor resection with microscopically negative margins (no residual tumor at the resection margin) (R0).

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

  2. 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.

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

  3. 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.

    Measured: 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.

  4. 3-year Disease-Free Survival (3y DFS)

    Proportion of participants who are alive without recurrence or metastasis within 3 years after surgery.

    Measured: Up to 3 years postoperatively.

  5. Safety (Neoadjuvant, Perioperative, and Follow-up Periods)

    Safety and tolerability assessed across study periods, including incidence of AEs/SAEs and treatment discontinuation due to AE/SAE.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2026
  2. Study start20 Apr 2026 (estimated)
  3. Primary completion31 Jul 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07549906
Sponsor's protocol ID
2025-FXY-242
Status last verified
Apr 2026
First submitted
6 Feb 2026
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Iparomlimab/Tuvonralimab, Capecitabine and Oxaliplatin in people with Colon Cancer (Stage II &Amp; III) and Immunotherapy, run by Sun Yat-sen University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Rongxin Zhang, MD, PhD (+86 020 87343920, zhangrx@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major Pathological Response (MPR) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07549906.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in