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

NCT07722754 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2024-373-05
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary endpoint: objective response rate Secondary endpoints: PFS, OS and adverse events

Conditions

Colorectal Neoplasms Malignant; Neoplasm, Metastatic

Keywords

Bevacizumab; Immune checkpoint inhibitors; Cetuximab; Irinotecan

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  the proportion of participants who achieved a complete or partial response according to RECIST 1.1

  12 months

Secondary Outcomes (3)

• Progression-free Survival

  12 months

• Overall Survival

  18 months

• Adverse Events

  18 months

Study Arms (2)

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.

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.

Drug: Cetuximab; Drug: Irinotecan; Drug: Bevacizumab; Drug: Sintilimab

Interventions

Cetuximab DRUG

250mg/m\^2/week with a loading dose of 400mg/m\^2

CI Arm; CIBS Arm

Irinotecan DRUG

125mg/m\^2 on D1 and D8 every three weeks

CI Arm; CIBS Arm

Bevacizumab DRUG

7.5mg/kg every three weeks

CIBS Arm

Sintilimab DRUG

200mg every three weeks

CIBS Arm

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Related Publications (1)

• 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.

  PMID: 35380713 BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm Metastasis

Interventions

Cetuximab; Irinotecan; Bevacizumab; sintilimab

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Jian Xiao, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Xiao, MD

CONTACT

86-20-83525975; xiaojian@gdph.org.cn

Xiaoru Lin

CONTACT

86-20-83525975; 13711114566@139.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: July 23, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share