Neoadjuvant Immunotherapy With Response-Adapted Treatment Versus Standard-of-Care Treatment for Resectable Stage III/IV Cutaneous Squamous Cell Carcinoma (C-PRE)

This study is for adults who have cutaneous squamous cell carcinoma (a type of skin cancer) that has grown into nearby tissue (stage III or stage IV) but can still be removed with surgery.

The purpose of this study is to compare the usual treatment alone with adding an immunotherapy medicine called cemiplimab (REGN2810, also known as Libtayo) to the usual treatment. The usual approach is surgery to remove the cancer, followed by more treatment such as radiation therapy if it is needed. In this study, some people receive cemiplimab before surgery. What happens after surgery is response-adapted, which means the treatment plan is based on how much the cancer shrank or changed in response to the medicine.

Researchers want to learn whether giving immunotherapy before surgery, and then adjusting treatment afterward based on the response, works better than the usual approach at keeping the cancer from coming back. They also want to learn more about the side effects of each approach and how people feel during and after treatment.

Taking part in a study is voluntary. People who join can talk with the study team about the possible risks and benefits and can leave the study at any time.

The study team decides who can join. In general, this study is looking for people who meet criteria like these:

• Adults 18 years of age and older
• Any sex
• A confirmed (biopsy-proven) diagnosis of invasive cutaneous squamous cell carcinoma (CSCC)
• Cancer that is stage III or stage IV and can be removed with surgery
• Previously untreated or recurrent CSCC
• A primary tumor in the head and neck skin area, the eyelid skin area, or another area of skin outside the head and neck
• Blood counts, kidney function, and liver function within the ranges set by the study
• Well enough to have surgery and the planned study treatment

Some health conditions and past treatments may keep a person from joining. Reasons someone may not be able to take part include:

• Squamous cell carcinoma that started in the mucous membranes (mucosal) rather than the skin
• Cancer that has spread to distant parts of the body
• Earlier treatment with an anti-PD-1 or anti-PD-L1 immunotherapy medicine
• An active autoimmune disease that needs treatment with medicines that affect the whole body
• A history of a solid organ transplant
• Other medical conditions that would make the study treatment unsafe

This is a general summary, not the complete list. The full eligibility criteria are decided by the study team and are listed on the ClinicalTrials government registry website under study number NCT06568172.

People who join this study are placed in one of the study groups by a computer, at random, like flipping a coin. Neither the participant nor the study doctor chooses the group.

Treatment

• One group receives the usual treatment: surgery to remove the cancer, followed by radiation therapy if the study doctor decides it is needed.
• The other group receives cemiplimab (Libtayo), an immunotherapy medicine given through a vein (IV), before surgery, and then has surgery.
• After surgery, treatment is response-adapted. The study team looks at how the cancer responded to the medicine and at the tissue removed during surgery, and then plans the next step. Depending on the response, this may mean more immunotherapy, radiation therapy, or careful monitoring without more treatment.

Tests and visits

Participants come to clinic visits before, during, and after treatment. During these visits, the study team checks on health and side effects and may do the following:

• Imaging scans, such as computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography with CT (PET/CT)
• Physical exams and blood samples
• Tissue samples from the tumor, including optional samples used for research
• Questionnaires about health, symptoms, and quality of life

Follow-up

After treatment ends, the study team continues to follow participants with regular visits, exams, and scans to see how they are doing and whether the cancer has come back. The length and timing of follow-up are explained in the consent form and by the study team.