Using Healthy Gut Bacteria to Boost Immune Treatment for Advanced Bowel Cancer

NCT07486492 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: XMYY-2026KY036
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research protocol outlines an exploratory study on the combination of early-life fecal microbiota transplantation (yFMT) with immunotherapy and chemotherapy in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). The single-center, single-arm study aims to assess the safety of yFMT in conjunction with immunotherapy and chemotherapy, with a secondary focus on exploring its efficacy and impact on the patients' immune microenvironment. The study will enroll 10 patients aged 18-75 who have progressed after first-line chemotherapy and targeted therapy. The intervention involves six sessions of yFMT every two weeks, alongside PD-1 inhibitor immunotherapy and FOLFIRI chemotherapy. The primary endpoints are the incidence of serious adverse events (SAEs), treatment-related adverse events (TRAEs), and intervention adjustments due to adverse events, while secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). The study is expected to last two years from initiation to data analysis completion, and it will be conducted at the Gastrointestinal Tumor Surgery Department of the First Affiliated Hospital of Xiamen University.

Conditions

Colorectal Cancer Metastatic; Fecal Microbiota Transplantation

Outcome Measures

Primary Outcomes (3)

• The incidence of serious adverse events (SAEs)

  The proportion of patients experiencing serious adverse events (Grade ≥3 per CTCAE v5.0) during the treatment and follow-up period, including events related to yFMT, immunotherapy, or chemotherapy that result in death, life-threatening conditions, hospitalization, or persistent disability.

  From the initiation of yFMT treatment to the completion of follow-up

• treatment-related adverse events (TRAEs)

  The incidence of adverse events assessed as related to the study intervention (yFMT, PD-1 inhibitor, or FOLFIRI regimen) by the investigator, graded according to CTCAE v5.0, occurring from treatment initiation through the follow-up period.

  From the initiation of yFMT treatment to the completion of follow-up

• the rate of intervention adjustments due to adverse events

  The proportion of patients requiring dose reduction, treatment interruption, or discontinuation of yFMT, immunotherapy, or chemotherapy due to treatment-related adverse events, documented with reasons and duration of adjustments.

  From the initiation of yFMT treatment to the completion of follow-up

Secondary Outcomes (3)

• PFS

  From treatment initiation to radiographic disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.

• ORR

  Objective response will be assessed every 6-8 weeks from the initiation of yFMT treatment until disease progression, death, or completion of 12-month study period (3-month treatment + 9-month follow-up), whichever occurs first.

• OS

  From treatment initiation until death (any cause) or last known alive date, up to 12 months.

Study Arms (1)

yFMT + PD-1 Inhibitor + FOLFIRI Group

EXPERIMENTAL

This study evaluates a combined intervention of young-donor fecal microbiota transplantation (yFMT), PD-1 inhibitor immunotherapy, and FOLFIRI chemotherapy for microsatellite stable metastatic colorectal cancer (MSS mCRC) patients. yFMT (6 sessions every 2 weeks via nasogastric tube or oral capsules) aims to modulate the gut microbiome and enhance immune response, administered concurrently with weight-based PD-1 inhibitor and FOLFIRI regimen (fluorouracil, leucovorin, irinotecan) synchronized every 2 weeks. This 3-month treatment period, followed by 9-month follow-up, tests the hypothesis that yFMT synergistically improves immunotherapy efficacy through microbiome alteration. Patients are closely monitored for adverse events with prompt management and regimen adjustments to ensure safety.

Drug: yFMT

Interventions

yFMT DRUG

This study evaluates a triple-combination therapy for MSS mCRC comprising: (1) yFMT (6 biweekly sessions via nasogastric tube or oral capsules using young-donor fecal microbiota to modulate gut microbiome); (2) weight-based PD-1 inhibitor immunotherapy; and (3) FOLFIRI chemotherapy (fluorouracil, leucovorin, irinotecan) synchronized biweekly with yFMT. The 3-month treatment period tests the hypothesis that yFMT enhances immunotherapy efficacy through microbiome-mediated immune modulation, followed by 9-month follow-up. Safety monitoring includes prompt adverse event management and regimen adjustments as needed.

Also known as: FOLFIRI Regimen, PD-1 Inhibitor

yFMT + PD-1 Inhibitor + FOLFIRI 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:

• Histologically or cytologically confirmed diagnosis of MSS mCRC
• Experienced disease progression after first-line chemotherapy and targeted therapy
• ECOG performance status of 0-1

You may not qualify if:

• History of FMT
• Severe organ dysfunction (heart, lung, liver, kidney)
• Other malignancies, psychiatric disorders, pregnancy or lactation
• Unable to provide informed consent

Sponsors & Collaborators

• The First Affiliated Hospital of Xiamen University: lead

Related Publications (9)

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 RESULT

• Wang FH, Zhang XT, Tang L, Wu Q, Cai MY, Li YF, Qu XJ, Qiu H, Zhang YJ, Ying JE, Zhang J, Sun LY, Lin RB, Wang C, Liu H, Qiu MZ, Guan WL, Rao SX, Ji JF, Xin Y, Sheng WQ, Xu HM, Zhou ZW, Zhou AP, Jin J, Yuan XL, Bi F, Liu TS, Liang H, Zhang YQ, Li GX, Liang J, Liu BR, Shen L, Li J, Xu RH. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond). 2024 Jan;44(1):127-172. doi: 10.1002/cac2.12516. Epub 2023 Dec 31.

  PMID: 38160327 RESULT

• Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

  PMID: 29097493 RESULT

• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5.

  PMID: 26541606 RESULT

• Zhao W, Lei J, Ke S, Chen Y, Xiao J, Tang Z, Wang L, Ren Y, Alnaggar M, Qiu H, Shi W, Yin L, Chen Y. Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215). EClinicalMedicine. 2023 Nov 14;66:102315. doi: 10.1016/j.eclinm.2023.102315. eCollection 2023 Dec.

  PMID: 38024475 RESULT

• Yu H, Li XX, Han X, Chen BX, Zhang XH, Gao S, Xu DQ, Wang Y, Gao ZK, Yu L, Zhu SL, Yao LC, Liu GR, Liu SL, Mu XQ. Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses. Front Microbiol. 2023 Apr 18;14:1126808. doi: 10.3389/fmicb.2023.1126808. eCollection 2023.

  PMID: 37143538 RESULT

• Davar D, Zarour HM. Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy. Clin Cancer Res. 2022 Oct 14;28(20):4370-4384. doi: 10.1158/1078-0432.CCR-21-1129.

  PMID: 35748749 RESULT

• De Lucia SS, Nista EC, Candelli M, Archilei S, Deutschbein F, Capuano E, Gasbarrini A, Franceschi F, Pignataro G. Microbiota and Pancreatic Cancer: New Therapeutic Frontiers Between Engineered Microbes, Metabolites and Non-Bacterial Components. Cancers (Basel). 2025 Nov 10;17(22):3618. doi: 10.3390/cancers17223618.

  PMID: 41300985 RESULT

• Zhu X, Hu M, Huang X, Li L, Lin X, Shao X, Li J, Du X, Zhang X, Sun R, Tong T, Ma Y, Ning L, Jiang Y, Zhang Y, Shao Y, Wang Z, Zhou Y, Ding J, Zhao Y, Xuan B, Zhang H, Zhang Y, Hong J, Fang JY, Xiao X, Shen B, He S, Chen H. Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses. Cell Metab. 2025 Apr 1;37(4):806-823.e6. doi: 10.1016/j.cmet.2024.12.013. Epub 2025 Feb 4.

  PMID: 39909032 RESULT

MeSH Terms

Interventions

Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Qingqi Hong, MD

  The First Affiliated Hospital of Xiamen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qingqi Hong, MD

CONTACT

15980809201; hqqsums@aliyun.com

Hongfei Huang

CONTACT

15159672193; 1378498011@qq.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Model Details: Intervention: Young-donor fecal microbiota transplantation (yFMT) combined with PD-1 inhibitor immunotherapy and FOLFIRI chemotherapy for MSS mCRC patients. yFMT: 6 sessions every 2 weeks (nasogastric tube or oral capsules) using fecal microbiota from young donors to modulate gut microbiome and enhance immune response. Immunotherapy: Weight-based PD-1 inhibitor to block the PD-1 pathway. Chemotherapy: FOLFIRI regimen (fluorouracil, leucovorin, irinotecan) every 2 weeks, synchronized with yFMT. Rationale: Synergistic approach where yFMT may improve immunotherapy efficacy by altering gut microbiome to enhance anti-tumor immune response. Duration: 3-month treatment period followed by 9-month follow-up. Safety: Close monitoring for adverse events with prompt management and regimen adjustments as needed. Objective: Explore yFMT's potential to enhance immunotherapy and chemotherapy effectiveness in MSS mCRC.

Study Record Dates

• First Submitted: March 14, 2026
• First Posted: March 20, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share