A Study of Setanaxib Co-Administered With Pembrolizumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN)

Inclusion Criteria

• Male or female patients aged ≥18 years, inclusive, at the time of informed consent.
• Willing and able to give informed consent and to comply with the requirements of the study.
• Histologically- or cytologically-confirmed diagnosis of SCCHN that is recurrent or metastatic with or without nodal involvement, and with or without metastatic spread, and is not eligible for surgical resection.
• Candidates for first-line treatment for pembrolizumab for recurrent or metastatic SCCHN, at the discretion of the investigator.
• A positive CAFs level (defined as CAFs level in tumours ≥5%), performed at a central laboratory, with fresh tumour biopsy taken during or within 30 days prior to the Screening Period. If available, suitable archival tissue (taken within 6 months prior to the Screening Visit and where the patient has received no further anti-cancer therapy during this 6-month period) can be used to assess tumour CAFs level and determine patient eligibility.
• Measurable disease, in accordance with RECIST v1.1, and with tumour accessible and of sufficient volume for pre-treatment and on-treatment biopsy.
• Combined positive score (CPS) ≥1, as determined on the archival or fresh tumour biopsy taken during or within 30 days prior to the Screening Period.
• HPV status known at randomisation.
• Life expectancy of at least 6 months in the judgment of the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and bone marrow function within 35 days of starting study treatment. Criteria "a" to "c" cannot be met in patients with ongoing or recent (within 14 days of screening test) transfusions or who require ongoing growth factor support:
• Absolute neutrophil count ≥1,000/mm3 (≥ 1.0×109/L).
• Platelet count ≥100,000/mm3 (≥ 100×109/L).
• Haemoglobin ≥9 g/dL, in the absence of transfusions for at least 2 weeks. Patients requiring ongoing transfusions or growth factor support to maintain haemoglobin ≥ 9g/dL are not eligible.
• Total bilirubin ≤1.5×upper limit of normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤3×ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN.
• Serum creatinine ≤2.0 mg/dL or creatinine clearance ≥40 mL/min (measured or calculated according to the method of Cockcroft and Gault).
• Female patients of childbearing potential must use a highly effective method of contraception to prevent pregnancy for ≥4 weeks before randomisation and must agree to continue strict contraception up to 120 days after the last dose of IMP or pembrolizumab, whichever is the later.
• For the purposes of this study, women of childbearing potential are defined as "fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy."
• Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In female patients who are not using hormonal contraception or hormonal replacement therapy but with suspected menopause and less than 12 months of amenorrhea, a high follicle stimulating hormone (FSH) level in the postmenopausal range will be required at Screening to confirm a postmenopausal state. Confirmation with more than one FSH measurement is required.
• Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly.
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline/Randomisation before dosing.
• Male patients with female partners of childbearing potential must be willing to use a condom and require their partner to use an a highly effective contraceptive method.
• Male patients must refrain from donating sperm, and female patients must refrain from donating eggs, from Baseline