Fecal Microbiota Transplantation Combined With NALIRIFOX Plus Serplulimab as First-line Treatment for Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.

NCT07854977 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IRB20260165
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This single center, prospective, randomized, open-label, two-arm parallel-controlled Phase II clinical trial is designed to evaluate the efficacy and safety of fecal microbiota transplantation （FMT ）combined with Nalirifox plus Serplulimab as first-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

Keywords

Fecal Microbial Transplantation; Nalirifox; Serplulimab; Liposomal Irinotecan; Oxaliplatin; Leucovorin; 5-Fluorouracil (5-FU)

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival （mPFS）

  The primary outcome will be median progression-free survival (mPFS), defined as the time from the date of first administration of study treatment to the first occurrence of objectively documented disease progression or death from any cause, whichever occurs first. mPFS will be used to evaluate the potential antitumor activity of FMT combined with Nalirifox plus serplulimab in treatment-naïve patients with locally advanced pancreatic ductal adenocarcinoma (PDAC). Tumor response and disease progression will be assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Radiographic assessments will be performed at baseline and subsequently every 9 weeks （±1 week） during the treatment period.

  From the first administration of study treatment dose of FMT until radiographic disease progression or death from any cause, whichever occurs first, up to approximately 1 year.

Secondary Outcomes (5)

• Objective Response Rate （ORR）

  From the first administration of study treatment dose of FMT until radiographic disease progression or death from any cause, whichever occurs first, up to approximately 1 year.

• Disease Control Rate （DCR）

  Starting from the first administration of study treatment dose of FMT to radiographic disease progression or death, up to approximately 1 year

• Duration of Response （DoR）

  Starting from the first administration of study treatment dose of FMT to radiographic disease progression or death, up to approximately 1 year.

• Overall Survival （OS）

  Starting from the first administration of study treatment dose of FMT to radiographic disease progression or death, up to approximately 1 year.

• Safety and Adverse Events

  30 days

Other Outcomes (2)

• Changes in patient gut microbiome composition following FMT

  At baseline, before Nalirifox plus Serplulimab administration on Day 8, before the second FMT administration on Day 29, and before the third FMT administration on Day 50.

• Multi-Omics prognosis biomarker Profiles

  At baseline, before Nalirifox plus Serplulimab administration on Day 8, before the second FMT administration on Day 29, and before the third FMT administration on Day 50.

Study Arms (2)

FMT+Chemotherapy+Immunotherapy

EXPERIMENTAL

Polyethylene glycol bowel preparation will be performed on Day 0, followed by FMT administration on Day 1. Starting on Day 8, Nalirifox will be administered intravenously once every 14 days, and serplulimab will be administered intravenously once every 3 weeks. Two additional FMT administrations will be given concurrently with ICI administration. For patients with stable or partial or complete response, the current treatment regimen will be continued in accordance with the study protocol.

Drug: FMT combined with chemotherapy plus immunotherapy

Chemotherapy+Immunotherapy

OTHER

Starting on Day 8, Nalirifox will be administered intravenously once every 14 days for 4 cycles, and serplulimab will be administered intravenously once every 3 weeks for 3 cycles. Two additional FMT administrations will be given concurrently with ICI administration.

Drug: Chemotherapy+Immunotherapy

Interventions

FMT combined with chemotherapy plus immunotherapy DRUG

Drug: Fecal Microbiota Transplantation * Fecal Microbiota Transplantation with 80- 100 g of healthy donor stool in 36-40 oral capsules Drug: NALIRIFOX Chemotherapy * Liposomal Irinotecan 50mg/m²/day IV for every two weeks * Oxaliplatin 60 mg/m²/day IV for every two weeks * Leucovorin 400 mg/m²/ day IV for every two weeks * 5-FU 2400 mg/ m² day IV for every two weeks Drug: Immunotherapy * Serplulimab 3mg/kg day IV for every three weeks

FMT+Chemotherapy+Immunotherapy

Chemotherapy+Immunotherapy DRUG

Drug: NALIRIFOX Chemotherapy * Liposomal Irinotecan 50mg/m²/day IV for every two weeks * Oxaliplatin 60 mg/m²/day IV for every two weeks * Leucovorin 400 mg/m²/ day IV for every two weeks * 5-FU 2400 mg/ m² day IV for every two weeks Drug: Immunotherapy * Serplulimab 3mg/kg day IV for every three weeks

Chemotherapy+Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma that is locally advanced, unresectable with no prior systemic therapy for advanced disease.
• At least one measurable lesion per RECIST v1.1.
• Adequate hematologic, hepatic, renal, and coagulation function per protocol-defined laboratory criteria, and no clinically significant electrocardiographic abnormalities.
• Able to swallow capsules whole, and no systemic broad-spectrum antibiotic use within the protocol-defined washout period prior to enrollment.
• ECOG performance status of 0 or 1, and life expectancy of at least 3 months

You may not qualify if:

• Patients with metastatic disease, peritoneal metastasis, malignant ascites, or unsuitable for NALIRIFOX treatment.
• Patients with active autoimmune diseases or requiring systemic immunosuppressive therapy and patients with immunodeficiency, HIV infection, or history of organ/hematopoietic stem cell transplantation.
• Patients with uncontrolled infection, active hepatitis B/C infection, or severe infectious diseases.
• Patients with gastrointestinal perforation, fistula, abscess, active bleeding, or contraindications to FMT.
• Patients with severe cardiac, hepatic, renal, or pulmonary dysfunction.
• Patients with known hypersensitivity to study drugs or FMT-related components.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

Location

Related Publications (19)

• Renouf DJ, Loree JM, Knox JJ, Topham JT, Kavan P, Jonker D, Welch S, Couture F, Lemay F, Tehfe M, Harb M, Aucoin N, Ko YJ, Tang PA, Ramjeesingh R, Meyers BM, Kim CA, Du P, Jia S, Schaeffer DF, Gill S, Tu D, O'Callaghan CJ. The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma. Nat Commun. 2022 Aug 26;13(1):5020. doi: 10.1038/s41467-022-32591-8.

  PMID: 36028483 BACKGROUND

• DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, Turbett S, Chung RT, Chen YB, Hohmann EL. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019 Nov 21;381(21):2043-2050. doi: 10.1056/NEJMoa1910437. Epub 2019 Oct 30.

  PMID: 31665575 BACKGROUND

• Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, Adler K, Dick-Necula D, Raskin S, Bloch N, Rotin D, Anafi L, Avivi C, Melnichenko J, Steinberg-Silman Y, Mamtani R, Harati H, Asher N, Shapira-Frommer R, Brosh-Nissimov T, Eshet Y, Ben-Simon S, Ziv O, Khan MAW, Amit M, Ajami NJ, Barshack I, Schachter J, Wargo JA, Koren O, Markel G, Boursi B. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021 Feb 5;371(6529):602-609. doi: 10.1126/science.abb5920. Epub 2020 Dec 10.

  PMID: 33303685 BACKGROUND

• Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin JM, Morrison RM, Deblasio RN, Menna C, Ding Q, Pagliano O, Zidi B, Zhang S, Badger JH, Vetizou M, Cole AM, Fernandes MR, Prescott S, Costa RGF, Balaji AK, Morgun A, Vujkovic-Cvijin I, Wang H, Borhani AA, Schwartz MB, Dubner HM, Ernst SJ, Rose A, Najjar YG, Belkaid Y, Kirkwood JM, Trinchieri G, Zarour HM. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595-602. doi: 10.1126/science.abf3363.

  PMID: 33542131 BACKGROUND

• Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, Thaiss CA, Reuben A, Livny J, Avraham R, Frederick DT, Ligorio M, Chatman K, Johnston SE, Mosher CM, Brandis A, Fuks G, Gurbatri C, Gopalakrishnan V, Kim M, Hurd MW, Katz M, Fleming J, Maitra A, Smith DA, Skalak M, Bu J, Michaud M, Trauger SA, Barshack I, Golan T, Sandbank J, Flaherty KT, Mandinova A, Garrett WS, Thayer SP, Ferrone CR, Huttenhower C, Bhatia SN, Gevers D, Wargo JA, Golub TR, Straussman R. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017 Sep 15;357(6356):1156-1160. doi: 10.1126/science.aah5043.

  PMID: 28912244 BACKGROUND

• Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, Quesada P, Sahin I, Chandra V, San Lucas A, Scheet P, Xu H, Hanash SM, Feng L, Burks JK, Do KA, Peterson CB, Nejman D, Tzeng CD, Kim MP, Sears CL, Ajami N, Petrosino J, Wood LD, Maitra A, Straussman R, Katz M, White JR, Jenq R, Wargo J, McAllister F. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019 Aug 8;178(4):795-806.e12. doi: 10.1016/j.cell.2019.07.008.

  PMID: 31398337 BACKGROUND

• Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE, Werba G, Zhang K, Guo Y, Li Q, Akkad N, Lall S, Wadowski B, Gutierrez J, Kochen Rossi JA, Herzog JW, Diskin B, Torres-Hernandez A, Leinwand J, Wang W, Taunk PS, Savadkar S, Janal M, Saxena A, Li X, Cohen D, Sartor RB, Saxena D, Miller G. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018 Apr;8(4):403-416. doi: 10.1158/2159-8290.CD-17-1134. Epub 2018 Mar 22.

  PMID: 29567829 BACKGROUND

• Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018 Jan 5;359(6371):104-108. doi: 10.1126/science.aao3290.

  PMID: 29302014 BACKGROUND

• 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 BACKGROUND

• Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragon L, Jacquelot N, Qu B, Ferrere G, Clemenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91-97. doi: 10.1126/science.aan3706. Epub 2017 Nov 2.

  PMID: 29097494 BACKGROUND

• Bear AS, Vonderheide RH, O'Hara MH. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell. 2020 Dec 14;38(6):788-802. doi: 10.1016/j.ccell.2020.08.004. Epub 2020 Sep 17.

  PMID: 32946773 BACKGROUND

• Ho WJ, Jaffee EM, Zheng L. The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities. Nat Rev Clin Oncol. 2020 Sep;17(9):527-540. doi: 10.1038/s41571-020-0363-5. Epub 2020 May 12.

  PMID: 32398706 BACKGROUND

• Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. doi: 10.1200/JCO.19.02105. Epub 2019 Nov 4.

  PMID: 31682550 BACKGROUND

• Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

  PMID: 28596308 BACKGROUND

• Wainberg ZA, M O'Reilly E. NALIRIFOX in the frontline for metastatic pancreatic cancer: evidence beyond NAPOLI 3. Nat Rev Clin Oncol. 2024 Dec;21(12):900-901. doi: 10.1038/s41571-024-00952-5. No abstract available.

  PMID: 39455872 BACKGROUND

• Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardiere C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1. Epub 2023 Sep 11.

  PMID: 37708904 BACKGROUND

• Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020 Jun 27;395(10242):2008-2020. doi: 10.1016/S0140-6736(20)30974-0.

  PMID: 32593337 BACKGROUND

• Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.

  PMID: 38230766 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Interventions

Drug Therapy; Immunotherapy

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Officials

• Hao Jihui, MD, PhD

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

• Zhang Ningning

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhang Ningning, MD, PhD

CONTACT

+8615822153931; mail4ningning@163.com

Yu Hao, PhD

CONTACT

+8613012284232; liuxiaotian116@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: October 2, 2026

Record last verified: 2026-09

Locations

CN (1)