NIVOLUMAB for Cutaneous squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 18 years of age or older\n- Patients willing and able to understand the Dutch study information and protocol requirements and comply with the treatment/intervention schedule, scheduled visits, and other requirements of the study.\n- UV-related stage I to IVa CSCC with an indication for extensive or disfiguring surgery  Stage III-IVa CSCC: T3-4N0-3M0 or T0N1-3M0  (Multi-focal) stage I-II CSCC\n- Primary tumour site:  Vermillion border lip (C00.0, C00.1, C00.2)  Skin of lip NOS (C44.0)  External ear (C44.2)  Skin face unspecified (ao: external lip and nasal vestibulum) (C44.3)  Skin scalp and neck (C44.4)  Overlapping lesion of skin (C44.8)  Primary site eyelid (C44.1)  Other body sites: CSCC outside head and neck area, but not vulva, anus or penis\n- World Health Organisation (WHO) performance status of 0-2\n- Indication for SOC surgery with curative intent ± RT\n- Screening laboratory values must meet the following criteria:  WBC ≥ 2.0x109 /L  Neutrophils ≥1.5x109 /L  Platelets ≥100 x109 /L  Haemoglobin ≥5.5 mmol/L  Creatinine ≤1.5x upper limit of normal (ULN)  AST ≤ 1.5 x ULN  ALT ≤ 1.5 x ULN  Bilirubin ≤1.5 X ULN (except patients with Gilbert Syndrome, who are eligible when total bilirubin < 3.0 mg/dL)\n- Women of child-bearing potential (WOCBP) must use appropriate method(s) of contraception. They should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required time for nivolumab to undergo five x T1/2) after the last dose of the IMP.\n- Women of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of ICB.\n- Men who are sexually active with WOCBP must use a contraceptive method with a failure rate of less than 1% per year and will be instructed to adhere to contraception for a period of 31 weeks after the last dose of ICB. Surgically sterile or azoospermic men do not require aforementioned contraception."}

Exclusion criteria

• {"criterion_text":"- Distantly metastasized (stadium IVb) CSCC\n- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids (up to 5 mg of prednisone per day is allowed)\n- Patients who are pregnant or breastfeeding\n- History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody\n- Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion\n- SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal portion of lip)\n- Patients for whom SOC consists of definitive (brachy)radiotherapy\n- Primary or recurrent CSCC appearing in an area that has been previously irradiated\n- Prior systemic therapy or immunotherapy.\n- Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)\n- Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)\n- Subjects with any active autoimmune disease or a documented history of autoimmune disease, except:  Subjects with vitiligo  Resolved childhood asthma/atopy  Residual hypothyroidism due to an autoimmune condition requiring only hormone replacement  Psoriasis not requiring systemic treatment  Any condition not expected to recur in the absence of an external trigger.\n- Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity or AEs"}

Primary endpoints

• {"endpoint_text":"- A clinical complete remission rate of at least 30% at 12, 18 and 24 months FU after only immunotherapy, without surgery, radiotherapy, or maintenance immunotherapy.","definition_or_measurement_approach":"A clinical complete remission (CCR) is diagnosed via routine physical examination, standard EORTC [18F]FDG-PET/CT criteria and is confirmed by pathological examination (no residual tumour cells in the biopsy and/or fine needle aspiration for cytology (FNAC))."}

Secondary endpoints

• {"endpoint_text":"- Rate and type of immune-related AEs (CTCAE v5.0, Clavien-Dindo);","definition_or_measurement_approach":"Adverse events assessed and graded using CTCAE v5.0 and Clavien-Dindo classification."}
• {"endpoint_text":"- Health-related QoL (EORTC QLQ-C30) between responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);","definition_or_measurement_approach":"Health-related quality of life measured using EORTC QLQ-C30 (and additional instruments listed in protocol such as H&N35, EQ5D, CWS, IT questionnaire and sexuality questionnaire)."}
• {"endpoint_text":"- Treatment duration and treatment stops;","definition_or_measurement_approach":"Duration of treatment and occurrences/duration of treatment interruptions/stops as recorded in study treatment records."}
• {"endpoint_text":"- Survival (DSS, RFS (RECIST v1.1), EFS and OS) at 12, 18 and 24 months FU;","definition_or_measurement_approach":"Survival endpoints include disease-specific survival (DSS), relapse-free survival (RFS) assessed per RECIST v1.1, event-free survival (EFS) and overall survival (OS) at specified follow-up timepoints."}
• {"endpoint_text":"- Survival of MATISSE 2 patients will also be compared to survival of a historic cohort of CSCC patients previously treated at the NKI-AVL with standard of care surgery ± RT without neoadjuvant immunotherapy;","definition_or_measurement_approach":"Comparative survival analysis versus a historic cohort from NKI-AVL (historic cohort data as recorded in institutional records)."}
• {"endpoint_text":"- Healthcare needs and consumption will be compared between MATISSE 2 responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);","definition_or_measurement_approach":"Healthcare utilisation and needs assessed and compared between responder and non-responder groups (methods as per protocol)."}
• {"endpoint_text":"- Healthcare utilisation of MATISSE 2 patients will also be compared to healthcare utilisation of a historic cohort of CSCC patients previously treated at the NKI-AVL with standard of care surgery ± RT without neoadjuvant immunotherapy;","definition_or_measurement_approach":"Comparison of healthcare utilisation metrics versus historic cohort from NKI-AVL."}
• {"endpoint_text":"- Cost-effectiveness will be assessed for MATISSE 2 responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);","definition_or_measurement_approach":"Cost-effectiveness analysis comparing responders and non-responders (methods described in protocol)."}
• {"endpoint_text":"- Costs of MATISSE 2 patients will be compared to costs of a historic cohort of CSCC patients previously treated at the NKI-AVL with standard of care surgery ± RT without neoadjuvant immunotherapy;","definition_or_measurement_approach":"Cost comparison versus historic cohort from NKI-AVL (cost data collection and analysis per protocol)."}

Netherlands

Earliest CTIS Part Ii Submission Date

16-12-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

462

Number Of Sites

5

Number Of Participants

41

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands