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

NCT ID: NCT04620200

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-11
• Study Completion Date: 2025-01-07

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.

Detailed Description

This is an investigator-initiated randomized non-comparative phase II trial consisting of 40 patients with resectable stage III-IVa CSCC randomized 1:1 to ARM A: 2 courses of nivolumab 3 mg/kg in week 0 and 2, or ARM B: 2 courses of nivolumab 3 mg/kg in week 0 and 2 plus 1 course of ipilimumab 1mg/kg in week 0. Both treatment arms are neo-adjuvant and applied prior to standard of care (consisting of surgery at week 4 with or without adjuvant radiotherapy).

Conditions

Cutaneous Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM A

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

3mg/kg

ARM B

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

3mg/kg

Ipilimumab

Intervention Type: DRUG

1mg/kg

Interventions

Nivolumab

3mg/kg

Intervention Type: DRUG

Ipilimumab

1mg/kg

Intervention Type: DRUG

Other Intervention Names

immunotherapy; immunotherapy

Eligibility Criteria

Inclusion Criteria

1. Age 18 years or older.

2. Patient is able to understand and comply with the protocol requirements and has signed the informed consent form.

3. World Health Organization (WHO) Performance Status 0 or 1 (Appendix B).

4. Patients with histologically or cytologically confirmed, primary or recurrent stage III-IVA CSCC of all body sites.

OR

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).

5. Eligible for standard-of-care, curatively intended surgery with or without adjuvant radiotherapy.

6. 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).

7. 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.

8. 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.

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 investigational product. Surgically sterile or azoospermic men do not require aforementioned contraception.

Exclusion Criteria

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 anti-CTLA4 or anti-PD1 immunotherapy.

6. Active human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

7. A 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 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.

9. 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.

10. A concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;

11. Pregnant or nursing.

12. A history of allergy to study drug components and/or a 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.

14. Use of prohibited medication at start of study period

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lotje Zuur, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

The Netherlands Cancer Institute

Locations

NKI-AVL

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

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 Oct 8. doi: 10.1038/s41591-025-03943-w. Online ahead of print.

Reference Type: DERIVED

PMID: 41062829 (View on PubMed)

Other Identifiers

N20MAT

Identifier Type: -

Identifier Source: org_study_id