Towards Cure Via Only Ultra-short ICB in CSCC (MATISSE 2)

Netherlands Cancer Institute (NKI)

Status and phase

Enrolling

Phase 2

Conditions

Cutaneous Squamous Cell Carcinoma

Cutaneous Squamous Cell Cancer

Cutaneous Squamous Cell Carcinoma (CSCC)

Cutaneous Squamous Cell Carcinoma of the Head and Neck

Treatments

Drug: Ipilumimab

Drug: Nivolumab

Study type

Interventional

Funder types

Other

Identifiers

NCT06823479

2024-516152-17-00 (EU Trial (CTIS) Number)

M24MAT

Details and patient eligibility

About

The goal of this clinical trial is to determine whether cutaneous squamous cell carcinoma patients can be cured using only immunotherapy, without surgery or radiotherapy.

Full description

This is an investigator-initiated phase 2 clinical trial consisting of 41 patients with stage I-IVa CSCC and an indication for morbid/extensive curative surgery. All patients will receive two courses of nivolumab 3 mg/kg in week 0 and week 2, and one course of ipilimumab 1 mg/kg in week 0. In week 5 response to immunotherapy will be evaluated using clinical examination, [18F]FDG-PET/CT imaging, regional lymph node ultrasound with FNAC (if applicable) and a multicentre multidisciplinary meeting. Non-responders will receive standard of care surgery (w/wo radiotherapy). Responders will enter a wait-and-monitor follow-up schedule in which response will be monitored every 3 months for a total of 2 years. If a patient is no longer responding to immunotherapy during follow-up they will receive standard of care surgery (w/wo radiotherapy).

Enrollment

41 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

18 years of age or older
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) or multi-focal stage I-II CSCC
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 vestibulum nasi) (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.
World Health Organisation (WHO) performance status of 0-2
Indication for SOC surgery with curative intent ± RT
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).
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.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of ICB.
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.

Exclusion criteria

Distantly metastasized (stadium IVb) CSCC
SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal portion of lip)
Patients for whom standard of care treatment consists of definitive (brachy)radiotherapy
Primary or recurrent CSCC appearing in an area that has been previously irradiated
Prior systemic therapy or immunotherapy.
Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)
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.
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
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)
Patients who are pregnant or breastfeeding
History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody
Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion.