Efficacy and Safety of AK104 Combined With Chemotherapy and Cetuximab or Bevacizumab

NCT07253896 | Recruiting Phase 2

• 1 other identifier: IR2023176
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Evaluate the objective response rate (ORR) of AK104 combined with chemotherapy and cetuximab or bevacizumab in second-line treatment of MSS type advanced colorectal cancer

Conditions

Safety

Keywords

colorectal cancer; AK104; chemotherapy; cetuximab; bevacizumab

Outcome Measures

Primary Outcomes (1)

• objective response rate

  The proportion of patients whose tumor volume has decreased by 30% and can be maintained for more than 4 weeks

  the proportion of lung cancer patients participating in clinical research who, after receiving treatment, achieve a significant reduction in tumor volume

Study Arms (1)

AK104 Combined With Chemotherapy and Cetuximab or Bevacizumab

EXPERIMENTAL

AK104 Combined With Chemotherapy and Cetuximab or Bevacizumab

Drug: AK104 and cetuximab or bevacizumab and FOLFIRI

Interventions

AK104 and cetuximab or bevacizumab and FOLFIRI DRUG

AK104 and cetuximab or bevacizumab and FOLFIRI as the second line

AK104 Combined With Chemotherapy and Cetuximab or Bevacizumab

Eligibility Criteria

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

You may qualify if:

• \. Voluntarily sign a written ICF. 2. Age at enrollment: ≥ 18 years old, ≤ 75 years old, both male and female. 3. The Eastern Cancer Collaborative Organization (ECOG) has a physical fitness score of 0 or 1.
• \. The expected survival period is ≥ 3 months. 5. Metastatic colorectal adenocarcinoma confirmed by histology or cytology. 6. Microsatellite instability (MSI) status is MSI-L or MSS type human. 7. The metastatic lesion cannot be removed and is not suitable for curative surgical treatment.
• \. Previously only received first-line systemic anti-tumor therapy based on oxaliplatin (FOLFOX or CAPOX), and other systemic anti-tumor treatments for metastatic colorectal cancer are not allowed. Note: For subjects who have previously received neoadjuvant therapy, adjuvant therapy, or curative radiotherapy and chemotherapy, if disease progression occurs during or within 6 months after treatment, it is considered that they have received first-line treatment.
• According to RECIST v1.1, subjects must have at least one measurable lesion. For subjects who have previously received radiotherapy, if there are no other lesions that can be selected as target lesions and there is objective evidence of significant progression after radiotherapy, the irradiated lesions can be considered as target lesions.
• \. The subjects are required to provide 15 recently archived or freshly obtained FFPE pathological sections of tumor tissue.
• \. Determine good organ function through the following requirements:
• a) Hematology (no use of any blood components or cell growth factor branches within 7 days prior to starting treatment)
• Holding treatment:
• i. Neutrophil absolute value ANC ≥ 1.5 × 109/L (1500/mm3); Ii. Platelet count ≥ 100 × 109/L (100000/mm3); Iii. Hemoglobin ≥ 90 g/L. b) Kidney: i. The calculated value of creatinine clearance rate \* (CrCl) is ≥ 50 mL/min
• \*The Cockcroft Fault formula will be used to calculate CrCl (Cockcroft Fault formula) CrCl (mL/min)={(140- age) × Weight (kg) × F} /(SCr (mg/dL) × 72) F=1 for males; F=0.85 for women; SCr=serum creatinine. Ii Urinary protein ≤ 1+or 24-hour (h) urinary protein quantification\<1.0 g. c) Liver: i. Total serum bilirubin (TBil) ≤ 1.5 × ULN; For liver metastasis or evidence to confirm/suspect Subjects with Gilbert disease, TBil ≤ 3 × ULN Ii. AST and ALT ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT ≤ 5 × ULN Iii. Serum albumin (ALB) ≥ 28 g/L d) Coagulation function: i. International Standardization Ratio

You may not qualify if:

• \. Patients with known MSI-H or dMMR. 2. Patients with BRAF mutations. 3. Subjects suffered from other malignant tumors within 3 years before enrollment, except for cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.).
• \. Simultaneously enroll in another clinical study, unless it is an observational, non-interference clinical study or a follow-up period of an intervention study.
• \. Have received any immunotherapy against tumors in the past, including immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any treatment targeting the immune mechanism of tumors.
• \. Patients with active autoimmune diseases that require systematic treatment within the past two years (such as using medication to improve the condition, corticosteroids, immunosuppressive agents), and replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) are not considered as systematic treatment.
• \. A history of active or previous inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
• \. History of immunodeficiency; HIV antibody test positive individuals; Currently using systemic corticosteroids or other immunosuppressants for a long time.
• \. Subjects who are known to have active pulmonary tuberculosis (TB) and suspected to have active TB need to undergo clinical examination to exclude them; Known active syphilis infection.
• \. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• \. Previous or current non infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid treatment.
• \. Severe infections occurring within 4 weeks prior to the first administration, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infections that have received systemic anti infective treatment within two weeks prior to the first administration (excluding antiviral treatment for hepatitis B or C).
• \. Active hepatitis C subjects (HCV antibody positive and HCV RNA levels above the detection limit).
• \. Those who have undergone major surgical procedures or experienced severe trauma within 30 days prior to the first administration, or have planned major surgical procedures within 30 days after the first administration (as determined by the investigator); Minor local surgery performed within 3 days prior to initial administration (excluding peripheral venous puncture and central venous catheterization and intravenous infusion port implantation)

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (2)

the Second Affiliated Hospital of Medical College of Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

the Second Affiliated Hospital of Medical College of Zhejiang University

Hangzhou, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ying Yuan, Dr

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuefeng Fang, Dr

CONTACT

0571-87784718; xffang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Second Affiliated Hospital, School of Medicine

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: November 28, 2025
• Study Start: January 3, 2024
• Primary Completion: January 3, 2026
• Study Completion (Estimated): January 3, 2027
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)