Colorectal Neoplasms MalignantPhase 2BOND-4NCT07722754
Bevacizumab, Sintilimab, Cetuximab and Irinotecan in Refractory RAS Wild-type Metastatic Colorectal Cancer: BOND-4 Trial
A Phase 2 study testing Cetuximab, Irinotecan and Bevacizumab in people with Colorectal Neoplasms Malignant and Neoplasm, Metastatic, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial summary
Primary endpoint: objective response rate Secondary endpoints: progression-free survival (PFS), overall survival (OS) and adverse events. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms Malignant, Neoplasm, Metastatic
- What is being tested?
- Cetuximab, Irinotecan and Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteChina
- Study dates
- 23 Jul 2026to 31 Jan 2029
- 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
- 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;
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- 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;
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510060
Xiaoru Lin, Bachelor, 81884713 ext. 80510, ruya16128@163.com
About this study
Official title: 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.
Read the 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 .
- Being tested
- Cetuximab, Irinotecan, Bevacizumab, Sintilimab
- Keywords
- Bevacizumab, Immune checkpoint inhibitors, Cetuximab, Irinotecan
- Medical subject headings
- Colonic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
250mg/m^2/week with a loading dose of 400mg/m^2
IrinotecanDrug
125mg/m^2 on D1 and D8 every three weeks
BevacizumabDrug
7.5mg/kg every three weeks
SintilimabDrug
200mg every three weeks
| Study group | Role | What they receive |
|---|---|---|
| CI Arm | Active comparator | Cetuximab: 250mg/m^2/week with a loading dose of 400mg/m^2; Irinotecan: 125mg/m^2 on D1 and D8 every three weeks. Receives: Drug: Cetuximab; Drug: Irinotecan |
| CIBS Arm | Experimental | 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. Receives: Drug: Cetuximab; Drug: Irinotecan; Drug: Bevacizumab; Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
the proportion of participants who achieved a complete or partial response according to RECIST 1.1
Measured: 12 months
Secondary outcomes (3)
Progression-free Survival
the interval from randomization to first disease progression or death from any cause or last follow-up
Measured: 12 months
Overall Survival
the interval from randomization to death from any cause or last follow-up
Measured: 18 months
Adverse Events
reported according to NCI Common Terminology Criteria for Adverse Events 5.0
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2026
- Study start23 Jul 2026
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal Neoplasms MalignantStudies of the same condition, open and under way.
- More trials run by Guangdong Provincial People's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jian Xiao, MD, Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07722754
- Sponsor's protocol ID
- KY2024-373-03
- Acronym
- BOND-4
- Status last verified
- Sep 2026
- First submitted
- 20 Jul 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lipsyc-Sharf M, Ou FS, Yurgelun MB, Rubinson DA, Schrag D, Dakhil SR, Stella PJ, Weckstein DJ, Wender DB, Faggen M, Zemla TJ, Heying EN, Schuetz SR, Noble S, Meyerhardt JA, Bekaii-Saab T, Fuchs CS, Ng K. Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. Oncologist. 2022 Apr 5;27(4):292-298. doi: 10.1093/oncolo/oyab025.
PubMed 35380713
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07722754
- Acronym / sponsor ID
- BOND-4 / KY2024-373-03
- Keywords
- Bevacizumab, Immune checkpoint inhibitors, Cetuximab, Irinotecan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Study start
- 23 Jul 2026 (actual)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 23 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary endpoint: objective response rate Secondary endpoints: progression-free survival (PFS), overall survival (OS) and adverse events.
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CI Arm | Active comparator | Drug: Cetuximab, Drug: IrinotecanCetuximab: 250mg/m^2/week with a loading dose of 400mg/m^2; Irinotecan: 125mg/m^2 on D1 and D8 every three weeks. |
| CIBS Arm | Experimental | Drug: Cetuximab, Drug: Irinotecan, Drug: Bevacizumab, Drug: SintilimabCetuximab: 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cetuximab250mg/m^2/week with a loading dose of 400mg/m^2 | Drug | CI Arm, CIBS Arm |
| Irinotecan125mg/m^2 on D1 and D8 every three weeks | Drug | CI Arm, CIBS Arm |
| Bevacizumab7.5mg/kg every three weeks | Drug | CIBS Arm |
| Sintilimab200mg every three weeks | Drug | CIBS Arm |
Primary outcome
Objective Response Rate
Time frame: 12 months
the proportion of participants who achieved a complete or partial response according to RECIST 1.1
3 secondary outcomes
Progression-free Survival
Time frame: 12 months
Overall Survival
Time frame: 18 months
Adverse Events
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Background: PubMed 35380713Lipsyc-Sharf M, Ou FS, Yurgelun MB, Rubinson DA, Schrag D, Dakhil SR, Stella PJ, Weckstein DJ, Wender DB, Faggen M, Zemla TJ, Heying EN, Schuetz SR, Noble S, Meyerhardt JA, Bekaii-Saab T, Fuchs CS, Ng K. Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. Oncologist. 2022 Apr 5;27(4):292-298. doi: 10.1093/oncolo/oyab025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jian Xiao, MD principal investigator
Guangdong Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab, Irinotecan and Bevacizumab in people with Colorectal Neoplasms Malignant and Neoplasm, Metastatic, run by Guangdong Provincial People's Hospital at 1 site in China.
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 13 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Jian Xiao, MD (86-20-83525975, xiaojian@gdph.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: 12 months). 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 NCT07722754, which also lists 1 linked publication.
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 Sep 2026.