Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients

NCT06280495 | Recruiting Phase 2

• 1 other identifier: INTENSIFY-CRC
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess whether the addition of Serplulimab (a PD-1 inhibitor) and Bevacizumab (an anti-angiogenesis agent) to the standard FOLFOX chemotherapy can enhance the immune microenvironment in the liver, increase T lymphocyte infiltration, and consequently improve the postoperative prognosis for patients with surgically resectable colorectal cancer liver metastases (RAS/BRAF wild-type, pMMR/MSS) compared to FOLFOX alone.

Conditions

Colorectal Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• 3-year Progression-Free Survival Rate

  The proportion of patients who, following the initiation of treatment, remain both alive and without evidence of disease progression for a consecutive period of three years.

  Assessed for three years following the initiation of treatment

Secondary Outcomes (6)

• Median Overall Survival

  Assessed throughout the study duration (5 years)

• Major Pathological Response (MPR)

  Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)

• Pathologic complete response (pCR)

  Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)

• Pathological Partial Response

  Assessed following neoadjuvant treatment and resection of CRLM (up to 5 years)

• Disease Free Survival

  Assessed throughout the study duration (5 years)

Study Arms (2)

FOLFOX only group

ACTIVE COMPARATOR

Oxaliplatin: 85 mg/m2 IV on day 1 Fluorouracil (FU): 400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours Leucovorin: 200 mg/m2 IV on day 1 This treatment regimen is repeated every two weeks for a total of 6 cycles.

Drug: Oxaliplatin; Drug: Fluorouracil

Serplulimab + Bevacizumab + FOLFOX

EXPERIMENTAL

Serplulimab: 200 mg IV infusion on day 1 Bevacizumab: 5 mg/kg IV infusion on day 1 Oxaliplatin, FU, and Leucovorin as per the control arm The experimental arm follows the same treatment schedule as the standard FOLFOX regimen, with the addition of Serplulimab and Bevacizumab for the first 3 cycles only.

Drug: Oxaliplatin; Drug: Fluorouracil; Drug: Serplulimab; Drug: Bevacizumab

Interventions

Oxaliplatin DRUG

5 mg/m2 IV on day 1

Also known as: Eloxatin

FOLFOX only group; Serplulimab + Bevacizumab + FOLFOX

Fluorouracil DRUG

400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours

Also known as: 5-FU

FOLFOX only group; Serplulimab + Bevacizumab + FOLFOX

Serplulimab DRUG

200 mg IV infusion on day 1

Also known as: anti-PD-1 antibody

Serplulimab + Bevacizumab + FOLFOX

Bevacizumab DRUG

5 mg/kg IV infusion on day 1

Also known as: Avastin

Serplulimab + Bevacizumab + FOLFOX

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; spartalizumab; 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)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yuhong Li, PhD

CONTACT

87342487; liyh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a prospective, randomized, multicenter clinical trial. Stratified randomization based on liver metastasis characteristics, including timing, number, and size, will be conducted in eligible patients.

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: February 28, 2024
• Study Start: February 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

CN (1)