Evaluation of Ipilimumab and Nivolumab in Immunotherapy for Cutaneous Squamous Cell Carcinoma in Patients Typically Undergoing Surgery and Radiotherapy
- Trial ID
- 2024-516152-17-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the rate of patients with a **clinical complete remission** at 12, 18, and 24 months of follow-up after treatment with only immunotherapy, without the use of surgery, radiotherapy, or maintenance immunotherapy, in patients with cutaneous squamous cell carcinoma. This objective is clinically relevant as it aims to evaluate the potential of immunotherapy to achieve remission while preserving organs and reducing the morbidity associated with traditional surgical and radiotherapeutic interventions.
Secondary objectives include:
- Assessing adverse events according to CTCAE v5.0 and immune-related CTCAE.
- Determining survival metrics such as disease-specific survival, relapse-free survival, event-free survival, and overall survival at 12, 18, and 24 months of follow-up.
- Evaluating health-related quality of life using instruments like EORTC QLQ-C30, H&N 35, EQ5D, CWS, IT questionnaire, and the sexuality questionnaire.
- Measuring treatment duration and treatment stops.
- Assessing healthcare utilization.
- Investigating cost-effectiveness.
Participants
The clinical trial focuses on patients diagnosed with **cutaneous squamous cell carcinoma**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a World Health Organisation (WHO) performance status of 0-2, indicating they are in relatively good health. The trial does not include a vulnerable population. Participants must be willing and able to understand the Dutch study information and comply with the study requirements. The trial population was selected based on specific inclusion criteria, such as having UV-related stage I to IVa CSCC with an indication for extensive or disfiguring surgery. Lifestyle considerations include the requirement for women of child-bearing potential to use appropriate contraception methods and for men who are sexually active with such women to adhere to contraceptive measures. Unfortunately, the sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **immunotherapy** in patients with cutaneous squamous cell carcinoma, aiming to achieve organ preservation and cure without the need for extensive surgery or radiotherapy. This is a Phase II, randomized, double-blind, controlled trial, with an estimated duration from January 2025 to January 2029. The trial involves the administration of two investigational medicinal products: YERVOY (ipilimumab) and OPDIVO (nivolumab), both delivered as a solution for infusion via intravenous administration. The primary objective is to determine the rate of clinical complete remission at 12, 18, and 24 months of follow-up after immunotherapy alone.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, performance status, and laboratory values. Following successful screening, participants will be randomized to receive the investigational products. The trial includes regular follow-up visits to monitor treatment response, adverse events, and overall health status. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination, which may be necessitated by adverse events, disease progression, or withdrawal of consent.
The expected length of participant involvement is up to 24 months, with conditions for early termination including significant adverse events or non-compliance with the study protocol. The trial aims to achieve a clinical complete remission rate of at least 30% at specified follow-up intervals, with secondary endpoints assessing immune-related adverse events, quality of life, treatment duration, and survival outcomes. The study will also compare healthcare utilization and cost-effectiveness between responders and non-responders, as well as against a historical cohort of patients treated with standard care.
Treatment
The clinical trial involves the administration of **YERVOY** (ipilimumab), a concentrate for solution for infusion, with a concentration of 5 mg/mL. This experimental medication is administered via **intravenous administration**. The dosing regimen for YERVOY is set at a maximum daily dose of 1 mg/kg, with a total maximum dose of 1 mg/kg over the treatment period. The treatment period for YERVOY is limited to 1 unit of time, as defined in the study protocol. The active substance, ipilimumab, is a protein of non-specific origin, and the product is manufactured by Bristol-Myers Squibb Pharma EEIG. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
Another experimental medication used in the trial is **OPDIVO** (nivolumab), also a concentrate for solution for infusion, with a concentration of 10 mg/mL. OPDIVO is administered intravenously, with a maximum daily dose of 3 mg/kg and a total maximum dose of 6 mg/kg over the treatment period. The treatment period for OPDIVO extends to 2 units of time, as specified in the study protocol. The active substance, nivolumab, is similarly a protein of non-specific origin, and the product is also produced by Bristol-Myers Squibb Pharma EEIG. Participant compliance with the dosing regimen is closely monitored to ensure protocol adherence.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial aims to evaluate the efficacy of immunotherapy alone in achieving clinical complete remission in patients with cutaneous squamous cell carcinoma, without the need for surgery, radiotherapy, or maintenance immunotherapy. The study protocol includes detailed monitoring of drug administration and participant compliance to ensure the integrity of the trial results.
Efficacy
Efficacy in the clinical trial titled "Towards organ preservation and cure via immunotherapy in cutaneous squamous cell carcinoma patients, normally undergoing extensive curative surgery and radiotherapy: Matisse-2" will be assessed using several parameters. The primary endpoint is the **clinical complete remission** rate, which is defined as achieving at least 30% remission at 12, 18, and 24 months of follow-up after immunotherapy alone, without the need for surgery, radiotherapy, or maintenance immunotherapy.
Secondary endpoints include the rate and type of immune-related adverse events, assessed using CTCAE v5.0 and Clavien-Dindo classifications. Health-related quality of life will be evaluated using the EORTC QLQ-C30 questionnaire, comparing responders who undergo only immunotherapy with non-responders who receive standard care after neoadjuvant immunotherapy. Additional secondary endpoints include treatment duration, treatment stops, and survival metrics such as disease-specific survival (DSS), recurrence-free survival (RFS) using RECIST v1.1, event-free survival (EFS), and overall survival (OS) at 12, 18, and 24 months of follow-up.
Comparative analyses will be conducted between MATISSE 2 patients and a historical cohort of cutaneous squamous cell carcinoma patients treated with standard care surgery with or without radiotherapy, focusing on survival, healthcare needs, healthcare utilization, and cost-effectiveness. These assessments will provide comprehensive insights into the efficacy of immunotherapy in this patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 (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 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
- 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.
- 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.
- 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.
- 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
- 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 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
- Use of other investigational drugs 30 days before study drug administration and 5 half times before study inclusion
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 01 Jan 2025 | — |
| Netherlands | — | — | 41 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OPDIVO 10 mg/mL concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 3 | 2 | PRD2941372 |
YERVOY 5 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS ADMINISTRATION | 1 | 1 | PRD2341715 |