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.
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 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
Parallel
Postbiotix-HLA™ is a food supplement based on fermented FOS from Lactobacillus paracasei CNCM I-5220 postbiotic.
Dietary supplementPostbiotix-HLA™, 1 capsule (400 mg) daily PO from cycle 1 day 1 up to cycle 5 day1 (i.e. 4 cycles);
placebo capsule
Dietary supplementAgente 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.
Pembolizumab
DrugPembrolizumab 200 mg q21 up to tumor progression, intolerable toxicities or 35 cycles (approximately 2 years of therapy).
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.
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
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.
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
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.
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