Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) MedDRA version: 26.1 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Calliditas Therapeutics Suisse SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged =18 years, inclusive, at the time of informed consent. 2. Willing and able to give informed consent and to comply with the requirements of the study. 3. Histologically- or cytologically-confirmed diagnosis of SCCHN (ie, primary tumour arising from the oral cavity [including tongue], nasal cavity, paranasal sinuses, oropharynx, hypopharynx, or larynx) that is recurrent or metastatic (including both HPV+ve and HPV-ve SCCHN), with or without nodal involvement, and with or without metastatic spread. 4. Candidates for first-line treatment for pembrolizumab for recurrent or metastatic SCCHN, at the discretion of the investigator. 5. A positive CAFs level (defined as CAFs level in tumours =5%), performed at a central laboratory, with a 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 (Note: patients found to have low CAF levels in archival tissue material should not proceed to have further biopsies or screening activities). 6. Measurable disease, in accordance with RECIST v1.1, and with tumour accessible and of sufficient volume for pre-treatment and on-treatment biopsy. 7. 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. 8. HPV status known at randomisation. 9. Life expectancy of at least 6 months in the judgment of the investigator. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 11. 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: a. Absolute neutrophil count =1,000/mm3 (= 1.0×109/L). b. Platelet count =100,000/mm3 (= 100×109/L). c. 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. d. Total bilirubin =1.5×upper limit of normal (ULN) (if associated with liver metastases or Gilbert's disease, =3×ULN). e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3×ULN. f. Serum creatinine =2.0 mg/dL or creatinine clearance =40 mL/min (measured or calculated according to the method of Cockcroft and Gault). 12. 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. a. 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." b. 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)
Exclusion criteria
Exclusion criteria: 1. Diagnosis of immunosuppression or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed. 2. Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1. 3. Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 (radiation therapy can be allowed for palliative therapy of bone metastasis only). 4. Not recovered from AEs Grade 2 or greater (except for alopecia) due to previously administered agents. 5. Treatment with any investigational agent within 12 weeks of Screening Visit or 5 half-lives of the IMP (if known), whichever is longer, or current enrolment in an interventional clinical study. 6. Prior treatment with setanaxib or participation in a previous setanaxib clinical study. 7. Prior treatment with pembrolizumab. 8. Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer that has undergone potentially curative therapy, or malignancy treated with curative intent and with no known active disease =2 years before the first dose of IMP and of low potential risk for recurrence. 9. Known active central nervous system metastases and/or carcinomatous meningitis. 10. Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents. The following are exceptions to this criterion: a. Patients with vitiligo or alopecia. b. Any chronic skin condition that does not require systemic therapy. c. Patients with coeliac disease controlled by diet alone. 11. Any evidence of current interstitial lung disease or pneumonitis, or a prior history of interstitial lung disease or non-infectious pneumonitis requiring high-dose glucocorticoids. 12. Active infection requiring systemic therapy. 13. Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Patients with a past or resolved hepatitis B virus infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of hepatitis B surface antigen [HBsAg]) are eligible provided the hepatitis virus DNA test is negative. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction (PCR) is negative for hepatitis C virus RNA. Patients with ongoing anti-viral therapy with potent inhibitors of cytochrome P450 (CYP) 3A4 are not eligible. Testing for HIV is only required if clinically indicated and is not mandatory for this study. 14. Serious chronic gastrointestinal conditions associated with diarrhoea. 15. History of significant haematological problems, such as blood dyscrasias requiring treatment, aplastic anaemia, myelodysplastic syndrome, or leukaemia. 16. Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the investigator). 17. A positive pregnancy test or breastfeeding for female patients. 18. Evidence of any of the following cardiac conduction abnormalities: a QTc Fredericia inter
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the change in tumour size per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab;Secondary Objective: - To compare the PFS per RECIST v1.1 in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab - To compare the change from Baseline in CAFs level in tumour tissue from recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab - To compare the change from Baseline in the number of CD8+ TILs and regulatory T-cells in tumour tissue from recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab;Primary end point(s): Best percentage change in tumour size, defined as the best percentage change from Baseline in the sum of diameters of target lesions, as assessed by RECIST v1.1;Timepoint(s) of evaluation of this end point: An initial data cut-off will occur approximately 9 weeks after completion of enrolment, when all patients are expected to have had at least 3 cycles of pembrolizumab, at least one post-treatment scan, and the opportunity for a post-treatment tumour biopsy. At this point, the primary endpoint of best percentage change in tumour size and some secondary endpoints will be analysed. An updated analysis may be performed after approximately 38 progression events have been reported allowing for approximately 65% maturity of the PFS data. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS, defined as time from randomisation to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. PFS at 3, 6, and 12 months and median PFS will be summarised • Change from Baseline in CAFs level in tumour tissue • Change from Baseline in CD8+ TILs and regulatory T-cells in tumour tissue ;Timepoint(s) of evaluation of this end point: Same as in E.5.1.1 | — |
Countries
France, Germany, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactLisa Bromley
ICON Clinical Research Limited
Outcome results
None listed