RecruitingPhase 2NCT07458529

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

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)

Sponsor

Seventh Medical Center of PLA General Hospital

Enrollment

50 participants

Start Date

Feb 10, 2026

Study Type

INTERVENTIONAL

Conditions

Neoadjuvant Therapy Immunotherapy Tislelizumab Rectal Cancer, Adenocarcinoma Probio-M9 Randomized

Summary

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria23

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 Criteria12

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

Interventions

COMBINATION_PRODUCTCRT+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.

COMBINATION_PRODUCTCRT+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.