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)

NCT07485296 | Recruiting Phase 2 DMC

• 1 other identifier: POST-BIO
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head & Neck Squamous Cell Carcinoma

Keywords

recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in HLA Class I-expressing circulating MDSCs

  2 years

• Change in circulating regulatory T cells (Tregs)

  2 years

• Change in tumor NLRC5 expression

  2 years

• Incidence and severity of treatment-related immune-related adverse events (irAEs)

  2 years

• Patient-reported treatment-related symptoms using NCI-PRO-CTCAE

  2 years

Study Arms (2)

Placebo Arm

PLACEBO COMPARATOR

* 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; Drug: Pembolizumab

Postbiotic Arm

ACTIVE COMPARATOR

* 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).

Dietary Supplement: Postbiotix-HLA™ is a food supplement based on fermented FOS from Lactobacillus paracasei CNCM I-5220 postbiotic.; Drug: Pembolizumab

Interventions

placebo capsule DIETARY_SUPPLEMENT

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.

Placebo Arm

Pembolizumab DRUG

Pembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).

Placebo Arm; Postbiotic Arm

Postbiotix-HLA™ is a food supplement based on fermented FOS from Lactobacillus paracasei CNCM I-5220 postbiotic. DIETARY_SUPPLEMENT

Postbiotix-HLA™, 1 capsule (400 mg) daily PO from cycle 1 day 1 up to cycle 5 day1 (i.e. 4 cycles);

Postbiotic Arm

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide informed consent for the trial and its procedure;
• Histological confirmation of HNSCC;
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) HNSCC;
• For oropharyngeal cancers, known IHC p16+ and/or ISH HPV status;
• Positive PD-L1 Combined Proportionate Score (CPS);
• Presence of neoplastic lesion deemed safely accessible for tumor biopsy by the investigator;
• No prior systemic therapy for RM HNSCC;
• Eligible to receive pembrolizumab as the standard of care
• ECOG Performance Status ≤ 2;
• Measurable disease as per RECIST 1.1;
• Males and females, ages ≥18;
• 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);
• 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);
• 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;
• 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;

You may not qualify if:

• 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.
• 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.
• 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.
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during the period of treatment.
• 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.
• Uncontrolled adrenal insufficiency.
• 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.
• Not recovered to ≤ Grade 1 toxicities related to any prior therapy before administration of study drug.
• Women who are pregnant or breastfeeding.
• 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
• Any of the following laboratory test findings:
• WBC \< 2,000/mm3
• Neutrophils \< 1,500/mm3
• Platelets \< 100,000/mm3

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, placebo controlled

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: March 20, 2026
• Study Start: January 27, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2032
• Last Updated: March 20, 2026

Record last verified: 2025-12

Locations

IT (1)