Postbiotix-HLA™ with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma.

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)

This trial will test whether taking the postbiotic supplement Postbiotix-HLA™ with first-line pembrolizumab reduces immune-related side effects and alters microbiota in people with recurrent or metastatic head and neck squamous cell carcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gruppo Oncologico del Nord-Ovest (Academic / other)
• Drugs / interventions: pembrolizumab, radiation, prednisone
• Locations: 1 site (Rozzano, Milano)
• Trial ID: NCT07485296 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase II trial enrolls patients with PD-L1–positive recurrent or metastatic head and neck squamous cell carcinoma who are starting pembrolizumab as first-line therapy. Participants are randomized to receive Postbiotix-HLA™ or matching placebo for four treatment cycles alongside standard pembrolizumab. The study will collect tumor biopsies, microbiome samples, and blood to measure changes in microbiota composition and systemic immune markers, while recording immune-related adverse events and clinical outcomes. The investigational product is a fermented FOS-based postbiotic derived from Lactobacillus paracasei CNCM I-5220 given as a food supplement rather than an additional drug.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed recurrent or metastatic PD-L1–positive head and neck squamous cell carcinoma, no prior systemic therapy for advanced disease, measurable disease, ECOG ≤2, and an accessible lesion for biopsy are ideal candidates.

Not a fit: Patients without PD-L1 expression, those ineligible for pembrolizumab, or those unable to undergo biopsy or with insufficient organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the postbiotic could reduce immune-related side effects from pembrolizumab and help patients remain on effective immunotherapy longer.

How similar studies have performed: Modulating the microbiome to reduce immunotherapy toxicity has shown promising signals in other cancer types but remains experimental and not yet proven in head and neck cancer.

Eligibility criteria

-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.

Where this trial is running

Rozzano, Milano

• Istituto Clinico Humanitas — Rozzano, Milano, Italy (Recruiting)

Conditions Head & Neck Squamous Cell Carcinoma; recurrent/metastatic head and neck squamous cell carcinoma