Towards organ preservation and cure via immunotherapy in cutaneous squamous cell carcinoma patients, normally undergoing morbid curative surgery and radiotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Apr 2025 → ongoing

Decision date (initial)

2025-01-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine the rate of patients with a clinical complete remission at 12, 18 and 24 months of FU after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy.

Secondary objectives 6

1. To assess adverse events (AE) according to CTCAE v5.0 and immune-related CTCAE;
2. To determine survival (DSS, relapse-free survival (RFS), event-free survival (EFS), overall survival (OS)) at 12, 18 and 24 months FU;
3. To evaluate health-related QoL (measured by EORTC QLQ-C30, H&N 35, EQ5D, CWS, IT questionnaire and the sexuality questionnaire);
4. To measure treatment duration and treatment stops;
5. To assess healthcare utilisation;
6. To investigate cost-effectiveness.

Conditions and MedDRA coding

Cutaneous squamous cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 18 years of age or older
2. 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
3. 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
4. World Health Organisation (WHO) performance status of 0-2
5. Indication for SOC surgery with curative intent ± RT
6. 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)
7. 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.
8. 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.
9. 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.
10. 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 13

1. Distantly metastasized (stadium IVb) CSCC
2. SCC localized in a mucosal surface (i.e. anus, vulva, penis or mucosal portion of lip)
3. Patients for whom SOC consists of definitive (brachy)radiotherapy
4. Primary or recurrent CSCC appearing in an area that has been previously irradiated
5. Prior systemic therapy or immunotherapy.
6. Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
7. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C antibody (HCV Ab)
8. 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.
9. 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
10. 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)
11. Patients who are pregnant or breastfeeding
12. History of allergy to study drug components and/or history of severe hypersensitivity to any monoclonal antibody
13. Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. Rate and type of immune-related AEs (CTCAE v5.0, Clavien-Dindo);
2. Health-related QoL (EORTC QLQ-C30) between responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);
3. Treatment duration and treatment stops;
4. Survival (DSS, RFS (RECIST v1.1), EFS and OS) at 12, 18 and 24 months FU;
5. 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;
6. Healthcare needs and consumption will be compared between MATISSE 2 responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);
7. 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;
8. Cost-effectiveness will be assessed for MATISSE 2 responders (undergoing only immunotherapy) and non-responders (undergoing standard of care after neoadjuvant immunotherapy);
9. 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;

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

C. Zuur

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

C. Zuur

Locations

1 EU/EEA country · 5 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

Documents 7 files

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

Application history

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