Modified Short-Course Radiotherapy Combined With Immunochemotherapy and Targeted Therapy as First-Line Treatment for MSS Metastatic Colorectal Cancer

A Clinical Study of Modified Short-Course Radiotherapy Combined With Tislelizumab, CAPOX Chemotherapy and Bevacizumab as First-Line Treatment for Initially Unresectable Microsatellite Stable Metastatic Colorectal Cancer

This is a single-arm interventional study targeting patients with initially unresectable MSS-type advanced colorectal cancer with liver and/or lung and peritoneal metastasis. Patients will receive lymph node-sparing modified short-course radiotherapy combined with tislelizumab, CAPOX chemotherapy, and bevacizumab targeted therapy, aiming to explore the tumor reactivity and safety of modified short-course radiotherapy combined with immunotherapy and first-line treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Patients With Initially Unresectable MSS-type Advanced Colorectal Cancer With Liver and/or Lung and Peritoneal Metastasis
• Intervention / Treatment: Drug: Receiving lymph node-sparing modified short-course radiotherapy combined with tislelizumab, CAPOX chemotherapy and bevacizumab targeted therapy

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Voluntarily participate in this study and provide written informed consent. Good compliance and ability to comply with follow-up procedures.

  2. Age ≥ 18 years. 3. Primary tumor located in the colon or rectum. 4. Histologically confirmed adenocarcinoma; pMMR by immunohistochemistry or MSS by genetic testing.

  5. Metastatic disease confirmed by contrast-enhanced or non-contrast CT or contrast-enhanced MRI within 3 weeks before enrollment; at least one measurable lesion in the liver and/or lung, or peritoneal cavity (RECIST 1.1); metastatic lesions assessed as initially unresectable by multidisciplinary discussion.

  6. ECOG performance status 0-1. 7. Life expectancy ≥ 3 months. 8. Adequate organ and bone marrow function:

  1. Hemoglobin ≥ 6.0 mmol/L,
  2. Absolute neutrophil count ≥ 1.5 ×10⁹/L,
  3. Platelet count ≥ 100 ×10⁹/L;
  4. Renal function: serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 30 mL/min;

  5. Hepatic function: serum bilirubin ≤ 2 × ULN, serum transaminases ≤ 5 × ULN. 9. No contraindications to surgery.

     Exclusion Criteria:

• 1. Prior treatment with PD-1, PD-L1, or other immune checkpoint inhibitors. 2. Prior receipt of any anti-tumor therapy for colorectal cancer, including radiotherapy, chemotherapy, or tumor resection surgery.

  3. Microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR).

  4. Presence of brain metastases. 5. Participation in another clinical trial of anti-tumor agents within 4 weeks prior to enrollment.

  6. History of hypersensitivity to monoclonal antibodies, any component of tislelizumab, capecitabine, oxaliplatin, or bevacizumab.

  7. Receipt of local treatments including transarterial chemoembolization, microwave ablation, radiofrequency ablation, SBRT, or metastasectomy for liver or lung metastases within 4 weeks prior to enrollment.

  8. Confirmed immunodeficiency disease or active autoimmune disease, including but not limited to systemic lupus erythematosus, inflammatory bowel disease, myasthenia gravis, autoimmune hepatitis, rheumatoid arthritis, multiple sclerosis, glomerulonephritis, vasculitis; use of other immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 4 weeks prior to enrollment.

  9. Known human immunodeficiency virus (HIV) infection; clinically significant liver disease including viral hepatitis [active HBV infection (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of detection)].

  10. Uncontrolled hypertension, or inadequate blood pressure control despite treatment with ≥ 3 antihypertensive agents.

  11. Disease with severe bleeding risk such as gastrointestinal bleeding, bleeding diathesis, or thrombotic disease requiring long-term oral anticoagulants or antiplatelet agents.

  12. Uncontrolled cardiac symptoms or diseases including but not limited to:

  1. NYHA class ≥ II heart failure;
  2. unstable angina;
  3. myocardial infarction within 1 year;

  4. clinically significant supraventricular or ventricular arrhythmias that are uncontrolled or poorly controlled despite intervention.

     13. Severe infection (CTCAE grade > 2) within 4 weeks prior to the first study drug administration, such as severe pneumonia, bacteremia, or infectious complications requiring hospitalization; active pulmonary inflammation on baseline chest imaging; signs or symptoms of infection or requirement for oral or intravenous antibiotics within 14 days before the first study drug administration (excluding prophylactic antibiotics); active tuberculosis confirmed by history or CT, history of active tuberculosis within 1 year prior to enrollment, or history of active tuberculosis more than 1 year prior without standard treatment.

     14. Diagnosis of another malignancy within 5 years prior to the first study drug administration, except malignancies with low risk of metastasis or death (5-year survival > 90%), such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.

     15. Pregnant or lactating female. 16. Other vulnerable populations, including patients with psychiatric disorders, cognitive impairment, or critical illness.

     17. Any other condition judged by the investigator that may lead to premature study discontinuation, such as other serious diseases (including psychiatric disorders) requiring concurrent treatment, alcoholism, drug abuse, family or social factors that may affect subject safety or compliance.

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: experimental arm; Lymph node-sparing modified short-course radiotherapy combined with tislelizumab, CAPOX chemotherapy and bevacizumab targeted therapy	Drug: Receiving lymph node-sparing modified short-course radiotherapy combined with tislelizumab, CAPOX chemotherapy and bevacizumab targeted therapy; Receiving lymph node-sparing modified short-course radiotherapy combined with tislelizumab, CAPOX chemotherapy and bevacizumab targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST criteria	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-Free Survival (PFS) is defined as the time from the date of first study treatment administration to the date of first documented disease progression or death from any cause, whichever occurs first	through study completion, an average of 1 year
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of patients who achieve confirmed complete response (CR), partial response (PR), or stable disease (SD) according to RECIST criteria.	through study completion, an average of 1 year
Safety of the study	Safety is evaluated by the incidence, severity, and relationship of adverse events, laboratory abnormalities and life state	Baseline and up to 8 weeks after completion of chemotherapy

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: tislelizumab
• Other Study ID Numbers: REACH-M

Drug and device information, study documents

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