Combining Serplulimab and Bevacizumab with FOLFOX for Colorectal Cancer Treatment

Neoadjuvant Combination of Serplulimab and Bevacizumab With FOLFOX Versus FOLFOX Alone for Resectable Liver Metastases in RAS/BRAF Wild-Type, pMMR/MSS Colorectal Cancer Patients

This study is testing if adding two new drugs to standard chemotherapy can help people with colorectal cancer that has spread to the liver live longer and have fewer chances of the cancer coming back after surgery.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 156 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Serplulimab, Bevacizumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06280495 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of adding Serplulimab, a PD-1 inhibitor, and Bevacizumab, an anti-angiogenesis agent, to the standard FOLFOX chemotherapy regimen for patients with surgically resectable colorectal cancer liver metastases. The study aims to enhance the immune microenvironment in the liver, increase T lymphocyte infiltration, and improve postoperative outcomes. Participants will be randomly assigned to receive either FOLFOX alone or the combination treatment, followed by surgical resection and regular follow-ups to assess treatment response and survival rates. The goal is to determine if the combination therapy leads to better recurrence-free survival and overall survival compared to standard treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed colorectal adenocarcinoma and resectable liver metastases.

Not a fit: Patients with extrahepatic metastases or those whose liver lesions are not resectable will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve postoperative prognosis and survival rates for patients with colorectal cancer liver metastases.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Age ≥18 and ≤75 years old
* Histologically confirmed colorectal adenocarcinoma
* Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
* Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, and pMMR/MSS
* Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
* Primary colorectal tumor has been or can be radically resected
* Liver metastatic lesions are resectable (including radiofrequency ablation and SBRT), and postoperative NED (no evidence of disease) is expected. Resectable liver metastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection can be performed (including radiofrequency ablation and SBRT); ③ Sufficient residual liver volume is expected after resection; ④ At least one hepatic vein can be preserved after resection, with preserved blood flow in and out of the residual liver and preserved bile ducts, and can preserve at least two adjacent liver segments; ⑤ No extrahepatic metastases.
* No prior anti-tumor therapy for liver metastases, except for surgical resection of primary lesions
* Normal hematological function (platelets \>90×109/L; white blood cells \>3×109/L; neutrophils \>1.5×109/L)
* Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 times ULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin ≥35g/L
* Liver function classified as Child-Pugh grade A
* Serum creatinine below the upper limit of normal (ULN), or calculated creatinine clearance rate \>50ml/min (using Cockcroft-Gault formula)
* ECOG performance status 0-1
* Expected lifespan \>3 months
* Signed written informed consent
* Willing and able to be followed up until death or end of study or study termination.

Exclusion Criteria:

* Diagnosis of colorectal cancer with distant extrahepatic metastases
* Prior chemotherapy, targeted therapy, intervention, or immunotherapy for liver metastases
* No planned surgical resection for liver metastatic lesions
* Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one year
* Any toxicity residuals from previous chemotherapy, excluding alopecia, such as peripheral neuropathy ≥NCI CTC v3.0 grade 2
* Use of immunosuppressive drugs one week prior to study treatment initiation, excluding topical corticosteroids via nasal, inhalational, or other routes or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day of prednisone or equivalent) or steroids used for prevention of contrast agent allergy
* Interstitial lung disease requiring corticosteroid treatment
* Known active autoimmune disease requiring symptomatic treatment or with a history of such disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia, or Graves' disease who have not required systemic treatment within the past 2 years, patients with hypothyroidism requiring only thyroid hormone replacement therapy, and patients with type I diabetes requiring only insulin replacement therapy can be included
* Known history of primary immunodeficiency
* Patients with active tuberculosis
* History of allogeneic organ or hematopoietic stem cell transplantation
* Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil, oxaliplatin) preparation or excipient component
* Bleeding tendency or coagulation disorder
* Significant symptoms of intestinal obstruction
* Hypertensive crisis or hypertensive encephalopathy
* Severe uncontrolled systemic complications such as infection or diabetes
* Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), hypertension that remains uncontrolled after appropriate drug treatment, unstable angina pectoris, congestive heart failure (NYHA 2-4), or arrhythmia requiring medication
* Past or physical examination showing central nervous system diseases (such as primary brain tumor, epilepsy uncontrolled by standard treatment, any history of brain metastasis, or stroke)
* Diagnosis of other malignant tumors within the past 5 years (excluding basal cell carcinoma and/or carcinoma in situ of the cervix after radical surgery)
* Patients who received any investigational drug therapy within the last 28 days prior to the study
* Pregnant or lactating women and women of childbearing age not using or refusing to use effective non-hormonal contraception (intrauterine devices, barrier contraception combined with spermicidal gel, or sterilization surgery) or men with reproductive potential unwilling or unable to comply with the study protocol

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Yuhong Li, PhD

Conditions Colorectal Cancer; Liver Metastases