Neoadjuvant Chemoradiotherapy Plus Tislelizumab With or Without Probio-M9 in pMMR/MSS Locally Advanced Rectal Cancer (NCRIT-PM9)

Neoadjuvant Chemoradiotherapy Combined With Tislelizumab With or Without Probio-M9 in pMMR/MSS Locally Advanced Middle and Low Rectal Cancer: A Single-Center, Prospective, Randomized Controlled Trial (NCRIT-PM9 Trial)

This prospective, single-center, randomized controlled trial aims to assessing the efficacy and safety of neoadjuvant chemoradiation plus Tislelizumab (PD-1 inhibitor) with or without Probio-M9 and subsequent TME surgery, by comparing assorted endpoints between two experiment groups (Experiment group 1: chemoradiation+PD-1 inhibitor+Probio-M9; Experiment group 2: chemoradiation+PD-1 inhibitor+placebo) with a control group (chemoradiation only).

Study Overview

• Status: Recruiting
• Conditions: Neoadjuvant Therapy; Randomized; Immunotherapy; Rectal Cancer, Adenocarcinoma; Tislelizumab; Probio-M9
• Intervention / Treatment: Combination product: CRT+PD-1 inhibitor+Probio-M9; Combination product: CRT+PD-1 inhibitor+placebo

Detailed Description

Patients with clinically staged II-III pMMR/MSS locally advanced rectal adenocarcinoma (≤10 cm from anal verge) will receive long-course chemoradiotherapy (50 Gy/25 fractions) with concurrent Capecitabine, followed by two cycles of CapeOX chemotherapy and Tislelizumab (200 mg IV every 3 weeks). Participants will be randomized to receive either daily oral Probio-M9 (2 g) or matched placebo from treatment initiation until surgery.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junfeng Du, PhD; Phone Number: +86-15810908850; Email: dujunfeng@301hospital.com.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100700
      • Recruiting
      • Seventh Medical Center of Chinese PLA General Hospital
      • Contact: Junfeng Du, PhD; Phone Number: +86 15810908850; Email: dujunfeng@301hospital.com.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• ECOG performance status 0-2
• Biopsy-proven rectal adenocarcinoma
• Distal tumor margin within 10 cm of the anal verge
• No distant metastasis
• Clinical stage II or III based on MRI (T4b excluded)
• Maximum diameter of rectal tumor ≥ 10 mm on baseline CT or MRI (measurable lesion according to RECIST 1.1)
• Willing and able to comply with the study protocol
• Willing to provide blood and tissue specimens for research purposes
• No prior anti-tumor treatment (e.g., radiotherapy, chemotherapy, immunotherapy, biological therapy, or herbal therapy)
• No history of immune system disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, thyroid autoimmune disease, ulcerative colitis, HIV infection, etc.)
• No significant dysfunction of major organs (heart, lung, liver, kidney)
• No jaundice or gastrointestinal obstruction
• No acute or ongoing infection

• Adequate hematologic and biochemical function including:

  • Neutrophils ≥ 1.5 × 10^9/L
  • Hemoglobin ≥ 80 g/L
  • Platelets ≥ 100 × 10^9/L
  • Serum creatinine ≤ 1.5 × ULN
  • Total bilirubin ≤ 1.5 × ULN
  • ALT and AST ≤ 2.5 × ULN
• No social or psychiatric disorders that may interfere with study participation
• Women of childbearing potential must have a negative pregnancy test before enrollment and must use effective contraception from study entry until 60 days after the last dose of study drug

Exclusion Criteria:

• History of multiple primary cancers or concomitant malignant tumors other than rectal cancer
• Receipt of any anti-cancer treatment (e.g., surgery, chemotherapy, radiotherapy, or other systemic therapies) within the past 5 years
• History of recent major surgery
• Conditions that may affect the gastrointestinal absorption of capecitabine (e.g., inability to swallow, persistent nausea or vomiting, chronic diarrhea)
• Uncontrolled or severe concomitant diseases of any kind
• Known allergy or hypersensitivity to any components of the study drugs
• Estimated life expectancy ≤ 5 years due to any cause
• Planned or prior organ or bone marrow transplantation
• Use of immunosuppressive therapy or systemic corticosteroids for immunosuppressive purposes within 1 month prior to enrollment
• History of central nervous system disorders that may impair the ability to provide informed consent or affect compliance with oral medication (investigator discretion)
• Other conditions that may interfere with study results or lead to premature discontinuation of study treatment (e.g., alcoholism or drug abuse)
• Pregnant or breastfeeding women, or women planning to become pregnant during the treatment period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRT+PD-1 inhibitor+Probio-M9	Combination product: CRT+PD-1 inhibitor+Probio-M9; Chemoradiation with PD-1 inhibitor (tislelizumab), with or without Probio-M9. Probio-M9 is administered orally at a dose of 2 g (one sachet) once daily. Treatment begins at the initiation of neoadjuvant chemoradiotherapy and continues until the day before surgical resection.
Placebo Comparator: CRT+PD-1 inhibitor+placebo	Combination product: CRT+PD-1 inhibitor+placebo; Chemoradiation with PD-1 inhibitor (tislelizumab) with placebo. Placebo is administered orally at a dose of 2 g (one sachet) once daily. Treatment begins at the initiation of neoadjuvant chemoradiotherapy and continues until the day before surgical resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	pathological complete response rate	within 10 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-y OS rate	2-year overall survival rate	2 year
2-y DFS rate	2-year disease free survival rate	2 year
3-y OS rate	3-year overall survival rate	3 year
3-y DFS rate	3-year disease free survival rate	3 year
5-y OS rate	5-year overall survival rate	5 year
5-y DFS rate	5-year disease free survival rate	5 year
immune-related adverse event rate	adverse event rate that is deemed to be associated with PD-1 inhibition	from commencing of PD-1 inhibition to the 30th day after surgery
Changes in Gut Microbiota Composition	Gut microbiota composition will be analyzed using metagenomic sequencing of stool samples. Fecal samples will be collected to evaluate microbial diversity, relative abundance of bacterial taxa, and functional pathway alterations during neoadjuvant treatment.	Stool samples will be collected at baseline (Day 1), Day 25 during treatment, and prior to surgery.

Collaborators and Investigators

• Sponsor: Seventh Medical Center of PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2026
• Primary Completion (Estimated): May 5, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: tislelizumab; locally advanced rectal cancer; Probio-M9
• 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; Molecular Mechanisms of Pharmacological Action; Therapeutics; Drug Therapy; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Radiotherapy; Combined Modality Therapy; Immune Checkpoint Inhibitors; Chemoradiotherapy; tislelizumab
• Other Study ID Numbers: S2026-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Export of individual patient data is a sensitive issue according to current Chinese laws

Drug and device information, study documents

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