Serplulimab Combined With CAPOX and Bevacizumab as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

A Single-Arm, Phase II, Multicenter Study of Serplulimab Combined With CAPOX Plus Bevacizumab as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

This is an exploratory study to evaluate the efficacy and safety of neoadjuvant therapy with serplulimab combined with CAPOX and bevacizumab for patients with locally advanced colorectal cancer. The primary endpoint is pathological complete response (pCR). Secondary efficacy endpoints include major pathological response (MPR), R0 resection rate, tumor down-staging, objective response rate (ORR), disease-free survival (DFS), and quality of life, to demonstrate clinical benefit of this combination regimen in the target patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Colorectal Cancer
• Intervention / Treatment: Drug: Serplulimab; Drug: CAPOX; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinqiang Liu; Phone Number: 19929061886; Email: ljq679@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily provide written informed consent prior to screening.
• Male or female subjects aged ≥18 years.
• At least one measurable lesion per RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically or pathologically confirmed locally advanced rectal adenocarcinoma, cT3/cT4N+M0 stage per AJCC/UICC 8th edition, with distance from anal verge ≤10 cm. Diagnosis is confirmed by contrast-enhanced CT/MRI, supplemented by colonoscopy and diagnostic laparoscopy if necessary; no prior anti-tumor treatment.
• Scheduled for surgical resection following neoadjuvant therapy based on clinical staging.
• Expected survival of more than 3 months.
• No emergency indications such as bowel obstruction, bleeding or perforation.

• Adequate major organ function as follows (no blood transfusion, granulocyte-colony stimulating factor (G-CSF) or other hematopoietic growth factor support within 14 days prior to screening):

  1. Hematology: Absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L, white blood cell count ≥3.5×10⁹/L.
  2. Liver function: ALT and AST ≤2.5×ULN; total bilirubin ≤1.5×ULN (≤3×ULN for patients with Gilbert syndrome).
  3. Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min.
  4. Coagulation function: APTT, INR, PT ≤1.5×ULN.

Exclusion Criteria:

• Prior anti-tumor therapy including chemotherapy, radiotherapy, hormonal therapy or molecular-targeted therapy.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibodies, or other agents targeting T-cell co-stimulatory or immune-checkpoint pathways.
• History of other malignant tumors within 5 years or concurrent other malignancies, except for cured carcinoma in situ of cervix, non-melanoma skin cancer, or other malignancies with ≥5 years disease-free survival after curative treatment.
• Peripheral neuropathy ≥Grade 2 per NCI-CTCAE v5.0.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• History of severe hypersensitivity reaction (NCI-CTCAE v5.0 ≥Grade 3) to anti-PD-1 monoclonal antibodies, other monoclonal antibodies, oxaliplatin, S-1 or related compounds.
• History of hereditary bleeding disorders or coagulopathy with high bleeding risk.
• Major surgical procedure within 4 weeks prior to screening.
• Not recovered from prior surgical complications with residual toxicity >Grade 1 (NCI-CTCAE v5.0), excluding alopecia and fatigue.

• Requirement for immunosuppressive medication within 2 weeks before screening or during study treatment, except for:

  1. Intranasal, inhaled, topical or intra-articular corticosteroids.
  2. Physiological-dose systemic corticosteroids (≤10 mg/day prednisone or equivalent).
  3. Short-term (≤7 days) corticosteroids for prophylaxis or treatment of non-autoimmune allergic conditions.
• Active or history of recurrent autoimmune disease.
• History of interstitial lung disease or non-infectious pneumonitis.
• Known active tuberculosis (Mycobacterium tuberculosis) infection.
• Human immunodeficiency virus (HIV) positive, other acquired or congenital immunodeficiency, history of organ transplantation or stem-cell transplantation.

• Hepatitis B or C virology findings at screening meeting any of the following:

  1. HBsAg-positive with HBV-DNA ≥10⁴ copies/mL or ≥2000 IU/mL (antiviral therapy may be administered for HBV carriers at investigator's discretion).
  2. Active hepatitis C: HCV-antibody-positive with detectable HCV-RNA above assay lower limit.
• Active or uncontrolled infection requiring systemic therapy within 2 weeks prior to screening.
• Receipt of live-virus vaccine within 4 weeks prior to screening.
• Bowel obstruction, or history of inflammatory bowel disease, extensive bowel resection with chronic diarrhea, Crohn's disease, ulcerative colitis or chronic diarrhea.
• Lactating females, or females planning pregnancy during study treatment or within 6 months after treatment completion.
• Subjects (fertile males, females and their male partners) unwilling to use effective contraception during study treatment and for 6 months after treatment completion.
• Any other condition that, in the investigator's opinion, would compromise study compliance or outcome assessment, making the subject unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Serplulimab plus CAPOX and Bevacizumab Neoadjuvant Treatment	Drug: Serplulimab; Anti-PD-1 monoclonal antibody, administered intravenously as neoadjuvant therapy.; Drug: CAPOX; Combination chemotherapy regimen consisting of capecitabine plus oxaliplatin, administered intravenously as neoadjuvant therapy.; Drug: Bevacizumab; Anti-VEGF monoclonal antibody, administered intravenously as neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	Percentage of patients who achieve pathological complete response, defined as no residual viable tumor cells in the resected surgical specimen.	Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) Rate	Percentage of patients with ≤10% residual viable tumor cells in the resected surgical specimen.	Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection)
R0 Resection Rate	Proportion of patients who undergo complete R0 surgical resection.	Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection)
Tumor Down-staging Rate	Proportion of patients with pathological tumor down-staging compared with baseline clinical staging.	Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection)
Objective Response Rate (ORR)	Proportion of patients with complete or partial response assessed by imaging according to RECIST criteria.	Up to 6 weeks after completion of neoadjuvant therapy (prior to surgical resection)
Disease-Free Survival (DFS)	Time from randomization/surgery to disease recurrence or death from any cause.	Up to 36 months after surgical resection

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Liu Hong, Xijing Hospital of Digestive Diseases, Xijing Hospital, Air force Medical University, Changlexi ST 15, Shaanxi Province, 710032, China

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 31, 2026
• First Submitted That Met QC Criteria: September 13, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Bevacizumab; CAPOX; Serplulimab
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: XJYY-LL-FJ-030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No