Effect of Postbiotics on Microbiota and Systemic Immunomodulation of Pembrolizumab as First-Line Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC) (POST-BIO)

A Phase II, Randomized, Double-blind, Placebo Controlled, Multicenter Pilot Study to Evaluate the Effect of Postbiotics on Microbiota and Systemic Immunomodulation of Pembrolizumab as First Line Standard of Care in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC)

phase II, randomized, double-blind, placebo controlled, non pharmacological clinical trial that aims to determine the effect of postbiotics Postbiotix-HLA™ on immuno-related adverse events (irAEs) in patients with recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC) treated with in first line pembrolizumab as standard of care (SoC).

The selected patient population will be randomised to receive the postbiotics Postbiotix-HLA™ or placebo for 4 cycles while in treatment with pembrolizumab as per clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Head & Neck Squamous Cell Carcinoma
• Intervention / Treatment: Dietary supplement: placebo capsule; Drug: Pembolizumab; Dietary supplement: Postbiotix-HLA™ is a food supplement based on fermented FOS from Lactobacillus paracasei CNCM I-5220 postbiotic.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
      • Contact: Carlo Resteghini; Phone Number: + 39 02 2390 2150; Email: carlo.resteghini@hunimed.eu
      • Principal Investigator: Carlo Resteghini

Participation Criteria

Eligibility Criteria

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

Description

-Inclusion Criteria

1. Be willing and able to provide informed consent for the trial and its procedure;
2. Histological confirmation of HNSCC;
3. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) HNSCC;
4. For oropharyngeal cancers, known IHC p16+ and/or ISH HPV status;
5. Positive PD-L1 Combined Proportionate Score (CPS);
6. Presence of neoplastic lesion deemed safely accessible for tumor biopsy by the investigator;
7. No prior systemic therapy for RM HNSCC;
8. Eligible to receive pembrolizumab as the standard of care
9. ECOG Performance Status ≤ 2;
10. Measurable disease as per RECIST 1.1;
11. Males and females, ages ≥18;
12. Adequate renal function defined as calculated creatinine clearance ≥30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or Serum creatinine < 1.5 x upper limit of normal (ULN);
13. Adequate liver function defined by AST or ALT < 3 x ULN (< 5 x ULN if liver metastases are present), and total bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg/dL);
14. Adequate bone marrow function defined by any of the following laboratory test findings: - WBC > 2,000/mm3, Neutrophils > 1,500/mm3, Platelets > 100,000/mm3;
15. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
16. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 6.3 and 6.4 - Contraception, for the course of the study through 120 days after the last dose of study medication; Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
17. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.3 and 6.4 - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; 18.

Willingness to provide blood, buccal swab samples, stool samples and tissue (if deemed safe by the investigator) for translational research.

- Exclusion Criteria

1. Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to >10 mg/day of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated.
2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
3. Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
4. Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
5. Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during the period of treatment.
6. Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
7. Uncontrolled adrenal insufficiency.
8. Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
9. Not recovered to ≤ Grade 1 toxicities related to any prior therapy before administration of study drug.
10. Women who are pregnant or breastfeeding.
11. History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry

12. Any of the following laboratory test findings:

    • WBC < 2,000/mm3
    • Neutrophils < 1,500/mm3
    • Platelets < 100,000/mm3
    • AST or ALT > 3 x ULN (> 5 x ULN if liver metastases are present)
    • Total bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 3.0 mg/dL)
    • Calculated creatinine clearance <30 millimeters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine >1.5 x upper limit of normal (ULN)
13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
14. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
15. Has a known history of active TB (Bacillus Tuberculosis)
16. Has previously received an organ transplant
17. Has previously received bone marrow transplantation
18. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Arm; Placebo 1 capsule (400 mg) daily PO from cycle 1 day 1 up to cycle 5 day1 (i.e. 4 cycles);; Pembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).	Dietary supplement: placebo capsule; Agente di carica: Mannitolo; Opercolo: Idrossipropilmetilcellulosa, Carbonato di calcio, Carragenina; Agente di carica: Cellulosa microcristallina; Agenti antiagglomeranti: Sali di magnesio di acidi grassi, Biossido di silicio.; Drug: Pembolizumab; Pembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).
Active Comparator: Postbiotic Arm; Postbiotix-HLA™, 1 capsule (400 mg) daily PO from cycle 1 day 1 up to cycle 5 day1 (i.e. 4 cycles); Pembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).	Drug: Pembolizumab; Pembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).; Dietary supplement: Postbiotix-HLA™ is a food supplement based on fermented FOS from Lactobacillus paracasei CNCM I-5220 postbiotic.; Postbiotix-HLA™, 1 capsule (400 mg) daily PO from cycle 1 day 1 up to cycle 5 day1 (i.e. 4 cycles);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in oral and fecal microbiota composition	Comparison of changes in the composition and diversity of microbiota in oral and fecal samples between treatment groups (pembrolizumab + Postbiotix-HLA™ vs pembrolizumab + placebo). Samples will be collected at baseline and Week 13. Microbiota composition will be analyzed using shotgun sequencing.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HLA Class I-expressing circulating MDSCs	Comparison of the proportion of HLA Class I - expressing circulating MDSCs from baseline to week 13 of therapy with pembrolizumab + Postbiotix-HLA™ vs pembrolizumab + placebo, measured by flow cytometry on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood samples	2 years
Change in circulating regulatory T cells (Tregs)	Comparison of the proportion of circulating Tregs from baseline to week 13 of therapy with pembrolizumab + Postbiotix-HLA™ vs pembrolizumab + placebo measured by flow cytometry on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood samples.	2 years
Change in tumor NLRC5 expression	Change in tumor expression level of NLRC5 from baseline to week 13 of therapy with Postbiotix-HLA™ + pembrolizumab vs pembrolizumab + placebo assessed on tumor tissue samples	2 years
Incidence and severity of treatment-related immune-related adverse events (irAEs)	Comparison of treatment-related irAEs between treatment groups (pembrolizumab + Postbiotix-HLA™ vs pembrolizumab + placebo), assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	2 years
Patient-reported treatment-related symptoms using NCI-PRO-CTCAE	Comparison of patient-reported treatment-related symptoms between treatment groups (pembrolizumab + Postbiotix-HLA™ vs pembrolizumab + placebo), assessed using the NCI PRO-CTCAE Items (Italian; Item Library Version 1.0). Patients will self-report symptom frequency, severity, and interference at each study visit using standardized questionnaires.	2 years

Collaborators and Investigators

• Sponsor: Gruppo Oncologico del Nord-Ovest

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Recurrence
• Other Study ID Numbers: POST-BIO

Drug and device information, study documents

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