Using immunotherapy to treat cutaneous squamous cell carcinoma without surgery

Towards Organ Preservation and Cure Via Immunotherapy in Cutaneous Squamous Cell Carcinoma Patients, Normally Undergoing Morbid Curative Surgery and Radiotherapy. The MATISSE 2 Trial, an Investigator-initiated Multicentre Phase 2 Trial

This study is testing if a combination of immunotherapy drugs can help patients with skin cancer avoid surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: nivolumab, immunotherapy, prednisone, ipilimumab
• Locations: 5 sites (Maastricht, Limburg and 4 other locations)
• Trial ID: NCT06823479 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial aims to evaluate the effectiveness of immunotherapy in curing patients with cutaneous squamous cell carcinoma (CSCC) without the need for surgery or radiotherapy. A total of 41 patients with stage I-IVa CSCC will receive two doses of nivolumab and one dose of ipilimumab. The patients' responses to the treatment will be assessed through clinical examinations and imaging techniques at week 5. Those who respond positively will be monitored for two years, while non-responders will receive standard surgical treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with UV-related stage I to IVa CSCC requiring extensive or disfiguring surgery.

Not a fit: Patients with CSCC not requiring extensive surgery or those with performance status above 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a non-invasive treatment option for patients with CSCC, potentially reducing the need for extensive surgeries.

How similar studies have performed: Other studies have shown promise in using immunotherapy for skin cancers, indicating potential success for this novel approach.

Eligibility criteria

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.

Where this trial is running

Maastricht, Limburg and 4 other locations

• Maastricht UMC — Maastricht, Limburg, Netherlands (Not_yet_recruiting)
• Netherlands Cancer Institute - Antoni van Leeuwenhoek — Amsterdam, North Holland, Netherlands (Recruiting)
• Amsterdam UMC — Amsterdam, North Holland, Netherlands (Not_yet_recruiting)
• Erasmus MC — Rotterdam, South Holland, Netherlands (Not_yet_recruiting)
• UMC Utrecht — Utrecht, Utrecht, Netherlands (Not_yet_recruiting)

Study contacts

• Principal investigator: Lotje Zuur, Prof. Dr. — The Netherlands Cancer Institute
• Study coordinator: Lotje Zuur, Prof. Dr.

Conditions Cutaneous Squamous Cell Carcinoma; Cutaneous Squamous Cell Cancer; Cutaneous Squamous Cell Carcinoma of the Head and Neck; nivolumab; opdivo; ipilimumab; yervoy; immunotherapy