A Series of Neoadjuvant Chemoradiotherapy Combined With Immunotherapy for Locally Advanced Rectal Cancer

A Series of Neoadjuvant Chemoradiotherapy Combined With Immunotherapy for Locally Advanced Rectal Cancer: From a Multicenter Phase II Cohort to a Phase III Randomized Controlled Study

The goal of this clinical trial is to compare the efficacy and safety of neoadjuvant chemoradiotherapy combined with tirelizumab compared with neoadjuvant chemoradiotherapy alone for neoadjuvant therapy in patients with locally advanced rectal cancer.

The main questions it aims to answer are:

To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with tirelizumab compared with neoadjuvant chemoradiotherapy alone for neoadjuvant therapy in patients with locally advanced rectal cancer To assess rectal or anal retention as well as quality of life. Participants will receive a long course of NCRT (50 Gy / 25f, capecitabine 850-1000 mg / m2, BID, PO, D1-D5, QW) within the first 5 weeks. In regard to tumor immunotherapy, enrolled patients will receive tislelizumab (200 mg, iv) on the first day at week 2,5, and 8 after initiation of radiotherapy. Thereafter, patients will be treated with two 14-day cycles of the CAPOX（Q 3 w; D1 oxaliplatin, 130mg/m2,iv.gtt; D1-D14, capecitabine, 850-1000mg / m2, BID, PO）regimen. Two CAOPX regimens were treated one week apart.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Carcinoma
• Intervention / Treatment: Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 375
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Zhongtao Zhang, MD; Phone Number: +86 13801060364; Email: Zhangzht@ccmu.edu.cn
• Study Contact Backup: Name: Hongwei Yao; Phone Number: +8613611015609; Email: yaohongwei@ccmu.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: Yao Hongwei, M.D; Phone Number: 86 13611015609; Email: yaohongwei@ccmu.edu.cn
    • Beijing, Beijing Municipality, China, 100050
      • Recruiting
      • Beijing Friendship Hospital
      • Contact: Zhongtao Zhang,, MD; Phone Number: +86-13801060364; Email: zhangzht@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed a written informed consent form and volunteered to join the study;
2. .Age: 18-75 years old, male or female;
3. Pathohistologically confirmed rectal adenocarcinoma, along with immunohistochemical results of pMMR or genetic test results of MSS;
4. The baseline clinical stage assessed by MRI was T1-2N1-2M0 or T3N0-2M0, MRF (-), lateral lymph nodes (-);
5. The lower tumor margin is 10cm away from the anal margin;
6. Surgical resection;
7. Ability to swallow tablets normally;
8. ECOG PS 0-1；
9. Have not received any anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;
10. Plan to undergo surgery after the completion of the neoadjuvant therapy;
11. No contraindications to surgery;
12. Main organ function is normal.

Exclusion Criteria:

1. Previous history of allergy to monoclonal antibodies, any component of tislelizumab,and capecitabine;

2. Previously has received or is receiving any of the following treatments:

   A)Any tumor-specific surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc; B)Treatment with immunosuppressive drugs or systemic hormones within 2 weeks of first use (dose> 10mg / day prednisone or equivalent dose); inhaled or topical steroids and dose> 10mg / day prednisone or equivalent dose of adrenocorticoid replacement in the absence of active autoimmune disease; C)Having received a live attenuated vaccine within 4 weeks before the first use of the study drug; D)Major surgery or severe trauma within 4 weeks before the first use of study drug;

3. History of any active autoimmune or autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered after hormone replacement therapy); patients with psoriasis or asthma / allergy in childhood and adults without any intervention, but patients requiring medical intervention with bronchodilators should not be included;
4. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disease, or a history of organ transplantation or allogeneic bone marrow transplantation;
5. Not well controlled cardiac clinical symptoms or disease, including but not limited to: such as (1) grade NYHA II above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinical meaningful supraventricular or ventricular arrhythmia without clinical intervention or clinical intervention still poor control;
6. Severe infection (Grade CTCAE> 2) within 4 weeks prior to the first use of study drug, Such as severe pneumonia, bacteremia, infection complications requiring hospitalization; Baseline chest imaging indicated the presence of active lung inflammation, presence of symptoms and signs and signs of infection within 14 days prior to the first administration of study drug or need for oral or intravenous antibiotics, Except for the preventive use of antibiotics; Found active tuberculosis infection by history or CT, Or those with a history of active tuberculosis infection within 1 year prior to enrollment, Or those with a history of active tuberculosis infection more than 1 year ago but without formal treatment;
7. Presence of active hepatitis B (HBV DNA 2000 IU / mL or 104copies / mL), hepatitis C (positive for hepatitis C antibody, and HCV RNA above the lower limit of detection of the analytical method);
8. A diagnosis of other malignancies within 5 years prior to the first use of study drug, unless a malignancy with low risk of metastasis or death (5-year survival> 90%), such as adequately treated skin basal cell carcinoma or squamous cell carcinoma in situ, are considered;
9. Women in pregnancy or lactation;
10. Other factors, as judged by the investigator, may lead to forced termination of the study, such as other serious illness (including mental illness), alcohol, substance abuse, family or social factors, which may affect the safety or compliance of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; The enrolled patients will receive a long course of NCRT (50 Gy / 25f, capecitabine 850-1000 mg / m2, BID, PO, D1-D5, QW) within the first 5 weeks. In regard to tumor immunotherapy, enrolled patients will receive tislelizumab (200 mg, iv) on the first day at week 2,5, and 8 after initiation of radiotherapy. Thereafter, patients will be treated with two 14-day cycles of the CAPOX（Q 3 w; D1 oxaliplatin, 130mg/m2,iv.gtt; D1-D14, capecitabine, 850-1000mg / m2, BID, PO）regimen. Two CAOPX regimens were treated one week apart. Eight to 8-10 weeks after the completion of radiation therapy, patients will undergo multiple examinations, including colonoscopy and MRI. Subsequent treatment options will be determined by each center physician based on their clinical experience.	Drug: Tislelizumab; Enrolled patients will receive tislelizumab 3 times after initiation of radiotherapy.
No Intervention: Control group; This group required only 5 weeks of NCRT and two 14-day cycles of the CAPOX （Q 3 w; D1 oxaliplatin, 130mg/m2,iv.gtt; D1-D14, capecitabine, 850-1000mg / m2, BID, PO）regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR	complete response rate=(number of pathological complete responses + number of clinical complete responses)/total number of patients	pCR :within 10 days after surgery;cCR :13 weeks after radiotherapy begins

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE rate	Adverse event rate	during treatment
NAR score	Neoadjuvant rectal（NAR）score：It is based on the scoring criteria of preoperative treatment	within 10 days after surgery
ORR	objective response rate objective response rate objective response rate objective response rate	within 10 days after surgery
OPR	organ preservation rate organ preservation rate organ preservation rate	immediately after surgery
immune-related adverse event rate	adverse event rate that is deemed to be associated with tislelizumab	up to 3 weeks after using tislelizumab

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Changhai Hospital; The First Affiliated Hospital of Anhui Medical University; Sun Yat-sen University; Fudan University; Peking Union Medical College Hospital; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; RenJi Hospital; West China Hospital; Peking University Cancer Hospital & Institute; The Affiliated Hospital of Qingdao University; Shandong Provincial Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Beijing Chao Yang Hospital; The First Affiliated Hospital of Zhengzhou University; Zhongnan Hospital; China-Japan Friendship Hospital; The First Hospital of Jilin University; Sixth Affiliated Hospital, Sun Yat-sen University; Queen Mary Hospital, Hong Kong; Tianjin Medical University General Hospital; Hebei Medical University Fourth Hospital; Sir Run Run Shaw Hospital; First Hospital of China Medical University; First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Shanxi Medical University; Sichuan Academy of Medical Sciences; First Affiliated Hospital of Chongqing Medical University; The University of Hong Kong-Shenzhen Hospital; Tianjin Union Medical Center; Zhejiang Tumor Hospital; Beijing Hospital of the Ministry of Health; Southern Medical University - Southern Hospital; Xijing Hospital of Airforce Medical University; Tangdu Hospital-Air Force Medical University; Daping Hospital, the Third Military Medical University; The Affiliated Tumour Hospital of China Academy of Medical Science; Rocket Force Characteristic Medical Center; The Second Affiliated Hospital of Naval Medical University; Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Taiwan Hexin Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 9, 2024
• First Submitted That Met QC Criteria: March 9, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; tislelizumab
• Other Study ID Numbers: BFH-niCRT-04

Drug and device information, study documents

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