Cutaneous Squamous Cell Carcinoma (CSCC)Phase 2MATISSE 2NCT06823479
Towards Cure Via Only Ultra-short ICB in CSCC
A Phase 2 study testing Nivolumab and Ipilumimab in people with Cutaneous Squamous Cell Carcinoma (CSCC) and Cutaneous Squamous Cell Cancer, run by The Netherlands Cancer Institute at 5 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Squamous Cell Carcinoma (CSCC), Cutaneous Squamous Cell Cancer, Cutaneous Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Nivolumab and Ipilumimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 5 sitesNetherlands
- Study dates
- 14 May 2025to Feb 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Recruiting
Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, North Holland, 1066CX
- Not yet recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105AZ
- Not yet recruiting
Maastricht UMC
Maastricht, Limburg, 6229HX
- Not yet recruiting
Erasmus MC
Rotterdam, South Holland, 3015GD
- Not yet recruiting
UMC Utrecht
Utrecht, Utrecht, 3584CX
About this study
Official title: 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
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.
Read the detailed 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).
- Conditions
- Cutaneous Squamous Cell Carcinoma (CSCC), Cutaneous Squamous Cell Cancer, Cutaneous Squamous Cell Carcinoma of the Head and Neck, Cutaneous Squamous Cell Carcinoma
- Being tested
- Nivolumab, Ipilumimab
- Keywords
- nivolumab, opdivo, ipilimumab, yervoy, immunotherapy, intravenous, checkpoint inhibitors, neoadjuvant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Immunotherapy
3 mg/kg
IpilumimabDrug
Also called Immunotherapy
1 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant nivolumab + ipilimumab | Experimental | Intravenous neoadjuvant nivolumab 3 mg/kg in week 0 and 2 in combination with intravenous neoadjuvant ipilimumab 1 m/kg in week 0. Receives: Drug: Nivolumab; Drug: Ipilumimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of clinical complete remission after only immunotherapy
The rate of patients with a clinical complete remission at 24 months of follow-up or at time of death prior to 24 months follow-up, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy.
Measured: From the start of immunotherapy until 24 months of follow-up
Secondary outcomes (16)
Rate of clinical complete remission after only immunotherapy
The rate of patients with a clinical complete remission at 12 and 18 months of follow-up or at time of death prior to the specified time-point, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy
Measured: From the start of immunotherapy until 12 and 18 months of follow-up.
Immune-related adverse events
The rate and type of immune-related adverse events (CTCAE v5.0, Clavien-Dindo).
Measured: From the start of immunotherapy until 100 days after the last course of immunotherapy.
Health-related quality of life (EORTC QLQ-C30)
EORTC Core Quality of Life questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate different domains. Functional and global health status scales indicated towards better levels of functioning, whereas higher scores in the symptom scales demonstrated higher levels of symptoms.
Measured: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EORTC QLQ-H&N35)
EORTC Head and Neck Cancer Quality of Life Questionnaire. Rated on a Likert-type scale from one (never) to four (almost always). Multi-item scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), and six symptom items (dental problems, opening mouth, dry mouth, sticky saliva, coughing, and feeling ill). Higher scores in the symptom scales demonstrated higher levels of symptoms.
Measured: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EQ5D)
EuroQol Five Dimensions Health Questionnaire. Domains: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. It also includes a VAS regarding patients' "Health Today" scored between 0 and 100. Each domain will be converted into categorical values (problems vs no problems).
Measured: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (CWS)
Cancer worry scale. Rated on a Likert-type scale from one (never) to four (almost always), which were summed to produce a total CWS score ranging from 8 to 32, with higher scores indicating more frequent worries about cancer.
Measured: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (IT)
Immunotherapy questionnaire. Rated on a Likert-type scale from one (never) to four (almost always), to evaluate toxicity after immunotherapy treatment.
Measured: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (sexuality questionnaire)
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate problems in sexual functioning.
Measured: From the start of immunotherapy until 24 months of follow-up.
Treatment duration
Total duration of received treatment
Measured: From the start of immunotherapy until the end of treatment (average 6 weeks)
Treatment stops
The amount of times and the length of time the immunotherapy, surgery or adjuvant radiotherapy had to be stopped.
Measured: From the start of immunotherapy until the end of treatment (average 6 weeks)
Disease-specific survival
The length of time a patient survives without death due to disease.
Measured: From the start of immunotherapy until 2 years follow-up.
Recurrence-free survival
The length of time a patient survives without recurrent disease.
Measured: From the start of immunotherapy until 2 years follow-up.
Event-free survival
The length of time a patient survives without recurrent disease or death of any cause.
Measured: From the start of immunotherapy until 2 years follow-up.
Overall survival
The length of time a patient survives after treatment.
Measured: From the start of immunotherapy until 2 years follow-up.
Healthcare consumption
Healthcare consumption during the trial.
Measured: From the start of immunotherapy until 24 months of follow-up.
Cost-effectiveness
The incremental cost-effectiveness ratio between quality-adjusted life years and the cost of trial-related healthcare.
Measured: From the start of immunotherapy until 24 months of follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2025
- Study start14 May 2025
- Primary completionFeb 2029 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Squamous Cell Carcinoma (CSCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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. If a patient is a non-responder to immunotherapy, they will receive standard of care surgery (w/wo radiotherapy).
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht, Erasmus Medical Center, Maastricht University Medical Center, Amsterdam UMC, location VUmc
- Responsible party
- Sponsor
- Investigators
- Lotje Zuur, Prof. Dr., Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06823479
- Sponsor's protocol ID
- M24MAT
- Other IDs
- 2024-516152-17-00
- Acronym
- MATISSE 2
- Status last verified
- May 2025
- First submitted
- 7 Jan 2025
- Last updated
- 29 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06823479
- Acronym / sponsor ID
- MATISSE 2 / M24MAT
- Conditions
- Cutaneous Squamous Cell Carcinoma (CSCC), Cutaneous Squamous Cell Cancer, Cutaneous Squamous Cell Carcinoma of the Head and Neck, Cutaneous Squamous Cell Carcinoma
- Keywords
- nivolumab, opdivo, ipilimumab, yervoy, immunotherapy, intravenous, checkpoint inhibitors, neoadjuvant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- UMC Utrecht, Erasmus Medical Center, Maastricht University Medical Center, Amsterdam UMC, location VUmc
- Study start
- 14 May 2025 (actual)
- Primary completion
- Feb 2029 (estimated)
- Study completion
- Feb 2029 (estimated)
- First posted
- 12 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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. If a patient is a non-responder to immunotherapy, they will receive standard of care surgery (w/wo radiotherapy).
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant nivolumab + ipilimumab | Experimental | Drug: Nivolumab, Drug: IpilumimabIntravenous neoadjuvant nivolumab 3 mg/kg in week 0 and 2 in combination with intravenous neoadjuvant ipilimumab 1 m/kg in week 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: Immunotherapy3 mg/kg | Drug | Neoadjuvant nivolumab + ipilimumab |
| IpilumimabAlso: Immunotherapy1 mg/kg | Drug | Neoadjuvant nivolumab + ipilimumab |
Primary outcome
Rate of clinical complete remission after only immunotherapy
Time frame: From the start of immunotherapy until 24 months of follow-up
The rate of patients with a clinical complete remission at 24 months of follow-up or at time of death prior to 24 months follow-up, whichever comes first, after only immunotherapy, without surgery, radiotherapy or maintenance immunotherapy.
16 secondary outcomes
Rate of clinical complete remission after only immunotherapy
Time frame: From the start of immunotherapy until 12 and 18 months of follow-up.
Immune-related adverse events
Time frame: From the start of immunotherapy until 100 days after the last course of immunotherapy.
Health-related quality of life (EORTC QLQ-C30)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EORTC QLQ-H&N35)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (EQ5D)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (CWS)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (IT)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Health-related quality of life (sexuality questionnaire)
Time frame: From the start of immunotherapy until 24 months of follow-up.
Treatment duration
Time frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
Treatment stops
Time frame: From the start of immunotherapy until the end of treatment (average 6 weeks)
Disease-specific survival
Time frame: From the start of immunotherapy until 2 years follow-up.
Recurrence-free survival
Time frame: From the start of immunotherapy until 2 years follow-up.
Event-free survival
Time frame: From the start of immunotherapy until 2 years follow-up.
Overall survival
Time frame: From the start of immunotherapy until 2 years follow-up.
Healthcare consumption
Time frame: From the start of immunotherapy until 24 months of follow-up.
Cost-effectiveness
Time frame: From the start of immunotherapy until 24 months of follow-up.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2025.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lotje Zuur, Prof. Dr. principal investigator
The Netherlands Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Ipilumimab in people with Cutaneous Squamous Cell Carcinoma (CSCC) and Cutaneous Squamous Cell Cancer, run by The Netherlands Cancer Institute at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lotje Zuur, Prof. Dr. (+31205129111, c.zuur@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of clinical complete remission after only immunotherapy (time frame: From the start of immunotherapy until 24 months of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025.