Towards Cure Via Only Ultra-short ICB in CSCC

NCT06823479 | Recruiting Phase 2

• 2 other identifiers: M24MAT2024-516152-17-00
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 5

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  From the start of immunotherapy until 24 months of follow-up

Secondary Outcomes (16)

• Rate of clinical complete remission after only immunotherapy

  From the start of immunotherapy until 12 and 18 months of follow-up.

• Immune-related adverse events

  From the start of immunotherapy until 100 days after the last course of immunotherapy.

• Health-related quality of life (EORTC QLQ-C30)

  From the start of immunotherapy until 24 months of follow-up.

• Health-related quality of life (EORTC QLQ-H&N35)

  From the start of immunotherapy until 24 months of follow-up.

• Health-related quality of life (EQ5D)

  From the start of immunotherapy until 24 months of follow-up.

Other Outcomes (8)

• Tumor micro-environment (IHC)

  From enrollment until week 5

• Tumor micro-environment (RNAseq)

  From enrollment until week 5

• Tumor micro-environment (spatial mass cytometry)

  From enrollment until week 5

Study Arms (1)

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.

Drug: Nivolumab; Drug: Ipilumimab

Interventions

Nivolumab DRUG

3 mg/kg

Also known as: Immunotherapy

Neoadjuvant nivolumab + ipilimumab

Ipilumimab DRUG

1 mg/kg

Also known as: Immunotherapy

Neoadjuvant nivolumab + ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• UMC Utrecht: collaborator
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (5)

Maastricht UMC

Maastricht, Limburg, 6229HX, Netherlands

NOT YET RECRUITING

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, North Holland, 1105AZ, Netherlands

NOT YET RECRUITING

Erasmus MC

Rotterdam, South Holland, 3015GD, Netherlands

NOT YET RECRUITING

UMC Utrecht

Utrecht, Utrecht, 3584CX, Netherlands

NOT YET RECRUITING

MeSH Terms

Interventions

Nivolumab; Immunotherapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Lotje Zuur, Prof. Dr.

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lotje Zuur, Prof. Dr.

CONTACT

+31205129111; c.zuur@nki.nl

Stan W. van Dijk, MD

CONTACT

+31205129111; matisse2@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: February 12, 2025
• Study Start: May 14, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

NL (5)