Adding tislelizumab with or without the probiotic Probio-M9 to pre-surgery chemoradiation for 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)
This will see if adding the PD-1 drug tislelizumab, with or without the probiotic Probio-M9, to standard pre-surgery chemoradiation helps adults with pMMR/MSS locally advanced rectal cancer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Seventh Medical Center of PLA General Hospital Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, Tislelizumab |
| Locations | 1 site (Beijing, Beijing Municipality) |
| Trial ID | NCT07458529 on ClinicalTrials.gov |
What this trial studies
Adults with clinically staged II–III pMMR/MSS rectal adenocarcinoma receive long-course chemoradiation with concurrent capecitabine, followed by two cycles of CapeOX chemotherapy and intravenous tislelizumab. Participants are randomized to daily oral Probio-M9 or matched placebo from treatment start until surgery, and all undergo total mesorectal excision (TME). The trial compares the two combination arms to a control arm receiving chemoradiation alone, monitoring safety, imaging and pathological response, and surgical outcomes. Outcomes will use RECIST/MRI and pathology to measure tumor shrinkage and treatment-related adverse events.
Who should consider this trial
Good fit: Adults (≥18) with biopsy‑proven, non‑metastatic stage II–III pMMR/MSS rectal adenocarcinoma within 10 cm of the anal verge, ECOG 0–2, measurable tumor, and no prior anti‑tumor therapy are the intended participants.
Not a fit: Patients with distant metastases, MSI‑high tumors, significant organ dysfunction, autoimmune/immune disorders, prior cancer treatment, or inability to undergo surgery are unlikely to qualify or benefit.
Why it matters
Potential benefit: If successful, the regimen could increase tumor response before surgery and may reduce the chance of recurrence.
How similar studies have performed: Combining immunotherapy with chemoradiation has shown promise mainly in MSI‑high rectal cancer and early-phase work, but using tislelizumab in pMMR/MSS disease and adding Probio-M9 is largely experimental.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Beijing, Beijing Municipality
- Seventh Medical Center of Chinese PLA General Hospital — Beijing, Beijing Municipality, China (Recruiting)
Study contacts
- Study coordinator: Junfeng Du, PhD
- Email: dujunfeng@301hospital.com.cn
- Phone: +86-15810908850
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.