Bevacizumab, Sintilimab, Cetuximab and Irinotecan in Refractory RAS Wild-type Metastatic Colorectal Cancer: BOND-4 Trial (BOND-4)

September 14, 2026 updated by: Guangdong Provincial People's Hospital

A Randomized, Multi-center, Open-label Phase II Trial of Irinotecan and Cetuximab With or Without the Combination of Bevacizumab and Sintilimab in RAS Wild-type, Irinotecan-refractory Metastatic Colorectal Cancer

Primary endpoint: objective response rate Secondary endpoints: progression-free survival (PFS), overall survival (OS) and adverse events.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This randomized, multi-center, open-label phase II trial studies the efficacy and safety of irinotecan and cetuximab with or without bevacizumab plus sintilimab in the treatment for RAS wild-type metastatic colorectal cancer (mCR) in third- or later-line setting.

Patients with refractory mCRC have limited treatment options after failure of standard chemotherapies and anti-angiogenic agents. The BOND-3 trial showed that adding bevacizumab to cetuximab and irinotecan may improve outcomes in this setting. Meanwhile, programmed death-1 (PD-1) inhibitors have demonstrated activity in MSI-high tumors but have limited efficacy in MSS mCRC. Preclinical and clinical evidence suggests that anti-VEGF therapy can modulate the tumor immune microenvironment and may synergize with PD-1 blockade. This study therefore tests whether the quadruple combination (bevacizumab + sintilimab + cetuximab + irinotecan) can improve objective response rate compared with cetuximab and irinotecan alone in this heavily pretreated population.

The primary efficacy analysis will be conducted on the intention-to-treat population. Assuming an ORR of 11% in the control arm and 26% in the experimental arm, with a one-sided alpha of 0.05 and power of 80%, the required sample size is approximately 160 to account for 5% dropout.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Guangdong Provincial People's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Metastatic and unresectable colorectal adenocarcinom;
  • RAS wild-type and MSS tumor;
  • Measurable lesions;
  • Failed to at least two lines of standard treatment containing fluoropyrimidine, irinotecan and bevacizumab;
  • Eastern Cooperative Oncology Group performance status 2 or less;
  • White blood cell≥ 3*10^9/L, neutrophil≥ 1.5*10^9/Lplatelet count≥75*10^9/L, hemoglobin≥60g/L;
  • Total serum bilirubin≤upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase ≤ 2.5*ULN or ≤5*ULN for subjects with liver metastasis;
  • Creatinine ≤ ULN or creatinine clearance ≥ 80 mL/min;
  • Urinary protein negative or 24-hour urinary protein ≤ 2g;
  • Activated partial thromboplastin time≤ULN and international normalized ratio≤1.5;
  • Any major surgery ≥ 4 weeks and any minor surgery ≥ 1 week and fully recovered from the procedure;
  • Life expectancy > 3 months;
  • Provide fully informed written consent;

Exclusion Criteria:

  • Other aggressive malignancies within 3 years (Exceptions: non-melanoma skin cancer or carcinoma-in-situ of the cervix that has been treated);
  • Allergy or intolerance to any of the study drugs;
  • Human immunodeficiency virus positive;
  • Concurrent anti-cancer therapy including radiation therapy, chemotherapy, targeted agents or biological agents not otherwise specified within two weeks;
  • Malignant bowel obstruction;
  • Prior treatment with PD-1 antibody;
  • Autoimmune diseases;
  • Significant bleeding events or pre-existing bleeding diathesis within 6 months (unless the source of bleeding has been resected);
  • Gastrointestinal perforation within 12 months;
  • Serious or non-healing wound, ulcer, or bone fracture;
  • Blood pressure >= 160/90 mmHg after active anti-hypertensive therapy;
  • Arterial or venous thrombotic or embolic events within 6 months (including but not limited to transient ischemic attack, cerebrovascular accident, unstable angina or myocardial infarction);
  • Uncontrolled illness including active infection, symptomatic congestive heart failure, cardiac arrhythmia, respiratory failure, symptomatic pulmonary fibrosis, interstitial pneumonitis or psychiatric illness that may interfere with the conduct of the study;
  • Known or suspected brain or central nervous system (CNS) metastases, or carcinomatous meningitis;
  • Any of the following: pregnant, nursing, childbearing potential but unwilling to employ contraception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CI Arm
Cetuximab: 250mg/m^2/week with a loading dose of 400mg/m^2; Irinotecan: 125mg/m^2 on D1 and D8 every three weeks.
Drug: Cetuximab
250mg/m^2/week with a loading dose of 400mg/m^2
Drug: Irinotecan
125mg/m^2 on D1 and D8 every three weeks
Experimental: CIBS Arm
Cetuximab: 250mg/m^2/week with a loading dose of 400mg/m^2; Irinotecan: 125mg/m^2 on D1 and D8 every three weeks; Bevacizumab: 7.5mg/kg every three weeks ; Sintilimab: 200mg every three weeks.
Drug: Cetuximab
250mg/m^2/week with a loading dose of 400mg/m^2
Drug: Irinotecan
125mg/m^2 on D1 and D8 every three weeks
Drug: Bevacizumab
7.5mg/kg every three weeks
Drug: Sintilimab
200mg every three weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: 12 months
the proportion of participants who achieved a complete or partial response according to RECIST 1.1
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: 12 months
the interval from randomization to first disease progression or death from any cause or last follow-up
12 months
Overall Survival
Time Frame: 18 months
the interval from randomization to death from any cause or last follow-up
18 months
Adverse Events
Time Frame: 18 months
reported according to NCI Common Terminology Criteria for Adverse Events 5.0
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangdong Provincial People's Hospital

Investigators

  • Principal Investigator: Jian Xiao, MD, Guangdong Provincial People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2026

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

January 31, 2029

Study Registration Dates

First Submitted

July 20, 2026

First Submitted That Met QC Criteria

July 20, 2026

First Posted (Actual)

July 23, 2026

Study Record Updates

Last Update Posted (Actual)

September 16, 2026

Last Update Submitted That Met QC Criteria

September 14, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY2024-373-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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