Tislelizumab With Fruquintinib, Metronidazole, in Mismatch Repair-proficient or Microsatellite Stability, Advanced Colorectal Cancer: a Multicenter, Single Arm, Clinical Trial

Division of Gastroenterology and Hepatology,Renji Hospital, School of Medicine, Shanghai Jiao Tong University

The aim of this study is to evaluate the efficacy and safety of Tislelizumab with Fruquintinib, Metronidazole treatment in MSS/MSI-L advanced colorectal cancer patients with high abundance of Fusobacterium nucleatum in a single arm Phase II clinical.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Tislelizumab with Fruquintinib, Metronidazole

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai First People's Hospital
  • Shanghai, China
    • Shanghai Ninth People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

1. No gender limit, age ≥ 18 years old and ≤ 80 years old
2. Colorectal cancer (AJCC stage IV) diagnosed by histological or cytological biopsy as metastatic or unresectable, with immunohistochemical or genetic testing indicating MSS or MSH-L type
3. Treatment requires third line or above, has previously received standard first and second line treatment, and the disease has progressed after treatment
4. Before accepting tirelizumab, qPCR should be used to detect the Fn CT value < 35 in fecal samples, and Fn is confirmed positive by agarose gel electrophoresis or Sanger sequencing
5. ECOG score: 0-1 points
6. Baseline blood routine and biochemical indicators meet the following criteria (no blood transfusion or use of colony stimulating factors 2 weeks prior to screening) Blood routine: hemoglobin ≥ 90g/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 100 × 109/L Liver function: ALT and AST ≤ 2.5 x ULN, serum total bilirubin ≤ 1.5 x ULN (if there is liver metastasis, ALT and AST ≤ 5 x ULN, serum total bilirubin ≤ 3 x ULN), serum albumin ≥ 30g/L Renal function: serum creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance rate ≥ 50 mL/min (calculated according to Cockcroft Gault formula). 7. Those who voluntarily participate in the trial and sign an informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab with Fruquintinib, Metronidazole	Drug: Tislelizumab with Fruquintinib, Metronidazole; Metronidazole tablets: One administration cycle is every 6 weeks, and metronidazole tablets are given orally on the 1st to 7th day of each cycle. The medication method is two tablets three times one day. Teralizumab: Every 3 weeks is a dosing cycle, with 200mg of Teralizumab administered intravenously on the first day of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-Free-Survival	The time from when the patient first receives immunotherapy and Metronidazole to the earliest evidence of disease progression，or date of death from any cause, whichever came first, assessed up to 100 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	The proportion of patients whose tumor volume has shrunk to a predetermined value (usually 30%) and can maintain the minimum time limit requirement is the sum of complete remissionand partial remission.
OS	Overall Survival	The time from when the patient first receives immunotherapy and Metronidazole to death, assessed up to 100 months.
DCR	Disease Control Rate	The proportion of patients whose tumors have achieved remission (PR+CR) and disease stability (SD, tumor shrinkage has not reached 30% but has not progressed) after treatment.

Collaborators and Investigators

• Sponsor: Jing-yuan Fang, MD, Ph. D

Publications and helpful links

General Publications

• Jiang SS, Xie YL, Xiao XY, Kang ZR, Lin XL, Zhang L, Li CS, Qian Y, Xu PP, Leng XX, Wang LW, Tu SP, Zhong M, Zhao G, Chen JX, Wang Z, Liu Q, Hong J, Chen HY, Chen YX, Fang JY. Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer. Cell Host Microbe. 2023 May 10;31(5):781-797.e9. doi: 10.1016/j.chom.2023.04.010. Epub 2023 May 1.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 12, 2027

Study Registration Dates

• First Submitted: April 5, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

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; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Nitroimidazoles; Nitro Compounds; Metronidazole; tislelizumab; HMPL-013
• Other Study ID Numbers: KY2024-004-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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