Akkermansia Probiotics Plus Anti-PD-1 Monoclonal Antibody in MSS/pMMR Advanced Colorectal Cancer

NCT06865521 | Active Not Recruiting

• 1 other identifier: AKPP-I 2025-2-21
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators propose to conduct a single-center, single-arm, Phase I clinical study to explore the safety and feasibility of Akkermansia probiotics combined with anti-PD-1 monoclonal antibody in patients with MSS/pMMR advanced colorectal cancer, as well as its impact on gut microbiota and the immune microenvironment.

Conditions

Colo-rectal Cancer; Akkermansia Muciniphila; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Physical Symptoms (Nausea, vomiting, headache, dizziness, fatigue, rash, itching, pain, etc); Laboratory Abnormalities: (Abnormal blood test results); Clinical Signs (ever, swelling, high blood pressure, low blood pressure, rapid heart rate, etc); Worsening of Pre-existing Conditions (xacerbation of a pre-existing disease or medical condition); New Medical Conditions (Development of new diseases or disorders that were not present before treatment); Psychological Effects (Anxiety, depression, insomnia, confusion, etc).

  From enrollment to one months after study exit

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  Up to 12 months

• Relative abundance of Akkermansia muciniphila (AKK) in fecal samples measured by qPCR

  Through study completion, an average of 2 months

• Quantitative analysis of peripheral blood immune cell subsets (CD8+ T cells, DC subtypes, MDSCs,, etc.) by flow cytometr

  Through study completion, an average of 2 months

• Serum cytokine profiling (IFN-γ, TNF-α, etc.) by ELISA

  Through study completion, an average of 2 months

• Changes in gut microbiome composition measured by 16S rRNA gene sequencing analysis

  Through study completion, an average of 2 months

Study Arms (1)

Self control group

OTHER

According to the inclusion and exclusion criteria, 22 patients will be recruited. After enrollment, patients will receive anti-PD-1 monoclonal antibody + Tyrosine kinase inhibitor (TKI, e.g., regorafenib, fruquintinib) treatment or anti-PD-1 monoclonal antibody ± chemotherapy (etc., CAPEOX \[oxaliplatin+capecitabine \], XELIRI \[irinotecan+capecitabine \]) ± Bevacizumab treatment (anti-PD-1 monoclonal antibody, chemotherapy, and bevacizumab every 3 weeks, TKI every 4 weeks), along with daily continuous administration of Akkermansia probiotics (Songke, dose: 1 capsule/day, taken with breakfast), until disease progression, intolerable toxicity, or patient withdrawal from the study.

Dietary Supplement: Akkermansia Probiotics

Interventions

Akkermansia Probiotics DIETARY_SUPPLEMENT

After enrollment, patients will receive anti-PD-1 monoclonal antibody + Tyrosine kinase inhibitor (TKI, e.g., regorafenib, fruquintinib) treatment or anti-PD-1 monoclonal antibody ± chemotherapy (etc., CAPEOX \[oxaliplatin+capecitabine \], XELIRI \[irinotecan+capecitabine \]) ± Bevacizumab treatment (anti-PD-1 monoclonal antibody, chemotherapy, and bevacizumab every 3 weeks, TKI every 4 weeks), along with daily continuous administration of Akkermansia probiotics (Songke, dose: 1 capsule/day, taken with breakfast), until disease progression, intolerable toxicity, or patient withdrawal from the study.

Self control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• ECOG performance status score of 0-2
• Histopathologically confirmed colorectal cancer; tumor tissue immunohistochemistry or genetic testing showing pMMR or MSS/MSI-L type
• Metastatic colorectal adenocarcinoma that has failed standard treatments (including irinotecan, oxaliplatin, fluorouracil, bevacizumab, cetuximab, etc.)
• No prior use of immunotherapy (such as immune checkpoint inhibitors, adoptive cell immunotherapy, etc.)
• At least one evaluable lesion according to RECIST version 1.1 criteria
• No intestinal obstruction and good oral compliance
• Adequate bone marrow, liver, and kidney function to receive treatment
• Signed informed consent

You may not qualify if:

• History of allergic diseases, severe drug allergies, or known allergies to probiotic drugs
• Use of antibiotics or probiotic drugs/health products within the last 3 months
• History of other malignancies with a disease-free interval of less than 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors cured by endoscopic mucosal resection)
• Presence of any active autoimmune disease or history of autoimmune disease
• Current use of immunosuppressants or hormone therapy, continued within 2 weeks prior to enrollment
• Concurrent severe infections
• Congenital or acquired immune deficiency, or active hepatitis
• Concurrent severe complications

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (2)

Colorectal Cancer, West China Hospital

Chengdu, Sichuan, 610041, China

Location

Colorectal Cancer, West China Hospital

Chengdu, Sichuan, China

Location

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: anti-PD-1 monoclonal antibody + TKI (TKI, e.g., regorafenib, fruquintinib) treatment / anti-PD-1 monoclonal antibody ± Chemotherapy (etc., CAPEOX, XELIRI) ± Bevacizumab treatment + Akkermansia probiotics

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 10, 2025
• Study Start: February 21, 2025
• Primary Completion: July 10, 2025
• Study Completion (Estimated): March 22, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (2)