The goal of this clinical trial is to learn if combining serplulimab (PD-1 inhibitor) with bevacizumab and short-course total neoadjuvant therapy (TNT) works to treat locally advanced mid-to-low rectal cancer in adults. It will also learn about the safety of this combination.
The main questions it aims to answer are:
Does adding bevacizumab to serplulimab and TNT increase the complete remission rate (cCR + pCR) compared with serplulimab and TNT alone? What medical problems do participants have when receiving these treatments?
Researchers will compare:
Experimental group: serplulimab + bevacizumab + chemotherapy + short-course radiotherapy Control group: serplulimab + chemotherapy + short-course radiotherapy
Participants will:
Receive either the experimental or control regimen for about 4-5 months before surgery or a watch-and-wait approach if complete response is achieved Undergo treatment in cycles that include chemotherapy, immunotherapy (and bevacizumab if in the experimental group), and short-course radiotherapy Visit the clinic regularly for check-ups, blood tests, imaging, endoscopy, and to monitor side effects Be followed for up to 5 years after treatment to assess cancer control, organ preservation, and survival outcomes
Age: 18 to 75 years old.
Diagnosis: Pathologically confirmed rectal adenocarcinoma with proficient mismatch repair (pMMR) / microsatellite stable (MSS) status, based on biopsy of the primary tumor.
Disease Stage: Untreated, preoperative clinical stage cT2-T4 and/or N+, M0 (AJCC 8th edition), unsuitable for initial local excision to achieve radical cure.
Tumor Location: Tumor within 8 cm from the anal verge, or assessed by surgeons as not suitable for immediate sphincter-preserving surgery.
Molecular Subtype: Rectal cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status.
Autoimmune Disease: Active, known, or suspected autoimmune disease.
Immunodeficiency: Known history of primary immunodeficiency.
Transplant History: History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
Parallel
Serplulimab
DrugSerplulimab 300 mg IV on Day 1
Bevacizumab
DrugBevacizumab 5 mg/kg IV on Day 1
Short-Course Radioterapy
Radiation25 Gy in 5 fractions over 1 week
Chemotherapy (CAPOX or capecitabine)
DrugCapecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle
Complete Remission (CR) Rate assessed by pathology, MRI, endoscopy, and clinical examination
Definition: The proportion of participants achieving complete remission, defined as: Pathologic complete response (pCR): No residual viable tumor cells detected in the resected specimen after neoadjuvant treatment (ypT0N0) Sustained clinical complete response (cCR): No evidence of residual tumor on digital rectal examination, endoscopy, and MRI, maintained for more than 1 year without surgery Assessment Method: Evaluated by investigators based on imaging, endoscopic findings, pathology (for surgical cases), and clinical examination
Organ Preservation Rate (OPR) assessed by MRI, endoscopy, and clinical examination
Definition: The proportion of participants who achieve organ preservation, defined as avoiding radical rectal resection (TME) without evidence of local tumor recurrence during follow-up. Assessment Method: Clinical examination, endoscopy, and MRI.
R0 Resection Rate confirmed by histopathology
Definition: The proportion of participants who undergo surgical resection with negative microscopic margins (no tumor cells at the resection margin). Assessment Method: Pathology review of surgical specimens.
Disease-Free Survival (DFS) measured by imaging and clinical follow-up
Definition: Time from randomization to documented disease recurrence (local or distant) or death from any cause, whichever occurs first. Assessment Method: Imaging, endoscopic examination, clinical records.
Overall Survival (OS) assessed by survival follow-up
Definition: Time from randomization to death from any cause. Assessment Method: Survival status by follow-up visits, phone calls, or registry data.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
