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.
• 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;
⁃ 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.
⁃ 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.