A research study to investigate the safety of setanaxib and helpfulness in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Calliditas Therapeutics Suisse S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Mar 2022 → 22 Aug 2025

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509917-35-00

EudraCT number

2021-004627-33

WHO UTN

U1111-1300-9549

ClinicalTrials.gov

NCT05323656

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacodynamic, Safety, Others, Pharmacokinetic

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 objectives 3

1. To compare the progression-free survival (PFS) per RECIST v1.1 in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab
2. To compare the change from Baseline in cancer-associated fibroblasts (CAFs) level in tumour tissue from recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab
3. To compare the change from Baseline in the number of cluster of differentiation 8 (CD8+) tumour-infiltrating lymphocytes (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

Conditions and MedDRA coding

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Male or female patients aged ≥18 years, inclusive, at the time of informed consent.
2. 2. Willing and able to give informed consent and to comply with the requirements of the study.
3. 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, and is not eligible for surgical resection.
4. 4. Candidates for first-line treatment for pembrolizumab for recurrent or metastatic SCCHN, at the discretion of the investigator.
5. 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. 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. 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. 8. HPV status known at randomisation.
9. 9. Life expectancy of at least 6 months in the judgment of the investigator.
10. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
11. 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). (For France: 1.500/mm3 [≥1.5×109/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). (For France: Serum creatinine ≤2.0 mg/dL and creatinine clearance ≥40 mL/min [measured or calculated according to the method of Cockcroft and Gault]).
12. 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) level in the postmenopausal range will be required at Screening to confirm a postmenopausal state. Confirmation with more than one FSH measurement is required. c. Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal) ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable) iii. Intrauterine device iv. Intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. Vasectomised partner vii. Sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception).
13. 13. 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.
14. 14. Male patients with female partners of childbearing potential must be willing to use a condom and require their partner to use a highly effective contraceptive method (as defined in the list in item 12c). Female condom and male condom should not be used together. This requirement begins at the time of informed consent and ends 120 days after receiving the last dose of IMP or pembrolizumab, whichever is the later.
15. 15. Male patients must refrain from donating sperm, and female patients must refrain from donating eggs, from Baseline until 120 days after the last dose of IMP or pembrolizumab, whichever is the later.

Exclusion criteria 27

1. 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. (For France: Patients with prior solid organ transplant or bone marrow transplant will be excluded).
2. 2. Anti-cancer monoclonal antibody treatment within 4 weeks prior to study Day 1.
3. 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. 4. Not recovered from AEs Grade 2 or greater (except for alopecia) due to previously administered agents.
5. 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. 6. Prior treatment with setanaxib or participation in a previous setanaxib clinical study.
7. 7. Prior treatment with pembrolizumab. (For France: Prior treatment with anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 [PD-L1] immune checkpoints drugs).
8. 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. 9. Known active central nervous system metastases and/or carcinomatous meningitis.
10. 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. 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. 12. Active infection requiring systemic therapy.
13. 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. 14. Serious chronic gastrointestinal conditions associated with diarrhoea.
15. 15. History of significant haematological problems, such as blood dyscrasias requiring treatment, aplastic anaemia, myelodysplastic syndrome, or leukaemia.
16. 16. Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the investigator).
17. 17. A positive pregnancy test or breastfeeding for female patients.
18. 18. Evidence of any of the following cardiac conduction abnormalities: a QTc Fredericia interval >450 milliseconds for male patients or >470 milliseconds for female patients. Patients with a second- or third-degree atrioventricular block are to be excluded.
19. 19. TSH >ULN at Screening.
20. 20. Unstable cardiovascular disease as defined by any of the following: a. Unstable angina within 6 months prior to Screening. b. Myocardial infarction, coronary artery bypass graft surgery, or coronary angioplasty within 6 months prior to Screening. c. Cerebrovascular accident within 6 months prior to Screening. d. New York Heart Association Class III or IV heart failure.
21. 21. Presence of any laboratory abnormality or condition that, in the opinion of the investigator, could interfere with or compromise a patient’s treatment, assessment, or compliance with the protocol and/or study procedures.
22. 22. Any other condition that, in the opinion of the investigator, constitutes a risk or contraindication for the participation of the patient in the study, or that could interfere with the study objectives, conduct, or evaluation.
23. 23. Use of medications known to be potent CYP3A4 inhibitors or inducers, or potent uridine diphosphate (UDP)-glucuronosyltransferase 1A9 (UGT1A9) inhibitors or inducers, within 21 days prior to IMP administration.
24. 24. Legal incapacity or limited legal capacity.
25. 25. Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
26. 26. Patients who are unable to provide informed consent, are incarcerated or unable to follow protocol requirements.
27. 27. Previous randomisation in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 3

1. 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
2. Change from Baseline in CAFs level in tumour tissue
3. Change from Baseline in the number of CD8+ TILs and regulatory T-cells in tumour tissue

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Calliditas Therapeutics Suisse S.A.

Sponsor organisation

Calliditas Therapeutics Suisse S.A.

Address

Chemin Des Aulx 14

City

Plan-Les-Ouates

Postcode

1228

Country

Switzerland

Scientific contact point

Organisation

Calliditas Therapeutics Suisse S.A.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Calliditas Therapeutics Suisse S.A.

Contact name

Clinical Trial Information Desk

Third parties 6

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications