Neo-adjuvant Nivolumab or Nivolumab With Ipilimumab in Advanced Cutaneous Squamous Cell Carcinoma Prior to Surgery

NCT04620200 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: N20MAT
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the histopathological response rate to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of standard of care(surgery ± radiotherapy).in patients with cutaneous squamous cell carcinoma.

Conditions

Cutaneous Squamous Cell Carcinoma

Keywords

immunotherapy; neoadjuvant; nivolumab; ipilimumab

Outcome Measures

Primary Outcomes (1)

• Histopathological response rate at standard of care

  The proportion of viable tumor cells left in the resected specimen, to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of SOC (surgery ± RT).

  At time of standard of care at week 4

Secondary Outcomes (12)

• Sensitivity and specificity of tumor biopsies, clinical photography, FDG-PET and (functional)MRI compared to the histopathological tumor response to neo-adjuvant immunotherapy

  At time of standard of care at week 4

• Numbers of participants without significant delay (>1 week) or cancelation of SOC surgery due to immune-related toxicity

  At time of standard of care at week 4

• Recurrence free survival (RFS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI

  At 2-years follow up

• Overall survival (OS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI

  At 2-years follow up

• The number of patients with AE (rate and type) acoording to NCI CTCAE v.5.0 up to 2 years FU after SOC

  At 2-years follow up

Study Arms (2)

ARM A

EXPERIMENTAL

2 courses of nivolumab 3 mg/kg in week 0 and 2 prior to standard of care

Drug: Nivolumab

ARM B

EXPERIMENTAL

2 courses of nivolumab 3 mg/kg in week 0 and 2 plus 1 course of ipilimumab 1mg/kg in week 0 prior to standard of care

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

3mg/kg

Also known as: immunotherapy

ARM A; ARM B

Ipilimumab DRUG

1mg/kg

Also known as: immunotherapy

ARM B

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older.
• Patient is able to understand and comply with the protocol requirements and has signed the informed consent form.
• World Health Organization (WHO) Performance Status 0 or 1 (Appendix B).
• Patients with histologically or cytologically confirmed, primary or recurrent stage III-IVA CSCC of all body sites.
• Patients with histologically or cytologically proven stage I-II CSCC, only in the case of:
• Presence of multifocal disease for which extensive and/or mutilating surgery is necessary (e.g. near-total scalp resection).
• Situated in an anatomical localization that necessitates extensive and/or mutilating surgery (e.g. orbital exenteration).
• Eligible for standard-of-care, curatively intended surgery with or without adjuvant radiotherapy.
• Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109 /L, Neutrophils ≥1.5x109 /L, Platelets ≥100 x109 /L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN (except subjects with Gilbert Syndrome, who are eligible when total bilirubin \< 3.0 mg/dL).
• Women of childbearing 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 for nivolumab to undergo five half-lives) after the last dose of the investigational drug.
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) prior to the start of nivolumab or nivolumab + ipilimumab.
• 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 investigational product. Surgically sterile or azoospermic men do not require aforementioned contraception.

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 SOC consists of definitive (brachy)radiotherapy.
• Primary or recurrent CSCC appearing in an area that has been previously irradiated.
• Prior anti-CTLA4 or anti-PD1 immunotherapy.
• Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• A 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 for:
• 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 study drug hazardous or obscure the interpretation of toxicity or AE.
• A concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

NKI-AVL

Amsterdam, North Holland, 1066CX, Netherlands

Location

Related Publications (1)

• Breukers SE, Traets JJH, van Dijk SW, Ostos MM, Fraterman I, Crommelin RD, van der Hulst H, Qiao X, Boere T, van de Poll-Franse LV, Retel V, van der Noort V, Vos JL, Toppenberg AGL, van der Heijden M, Missale F, Balm F, van den Brekel M, Dirven R, Karakullukcu MB, Karssemakers L, Klop WMC, Lohuis PJFM, Schreuder WH, Smeele LE, van der Velden LA, Plasmeijer E, Smit LA, de Boer JP, Navran A, Westerink B, de Koekkoek-Doll PK, Castelijns J, Wondergem M, Vogel WV, Kuijpers A, van Houdt WJ, Onderwater S, Maas-Bannink E, Cornelissen S, Broeks A, Tijink BM, Devriese LA, de Bree R, Blank CU, Schumacher TN, Thommen DS, Haanen JBAG, Zuur CL. Neoadjuvant ipilimumab and nivolumab in resectable cutaneous squamous cell carcinoma: a randomized phase 2 trial. Nat Med. 2025 Dec;31(12):4055-4064. doi: 10.1038/s41591-025-03943-w. Epub 2025 Oct 8.

  PMID: 41062829 DERIVED

MeSH Terms

Interventions

Nivolumab; Immunotherapy; Ipilimumab

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, MD, PHD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: November 6, 2020
• Study Start: August 11, 2020
• Primary Completion: January 7, 2025
• Study Completion: January 7, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)