Title
Randomized Phase III Trial of Neoadjuvant Immunotherapy With Response-Adapted Treatment Versus Standard-Of-Care Treatment for Resectable Stage III/Iv Cutaneous Squamous Cell Carcinoma

Description
OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 84 days of surgery, patients may undergo image-guided radiation therapy (IGRT) with intensity modulated radiation therapy (IMRT) for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

ARM 2: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo response-adaptive surgery 21 days after last dose of cemiplimab. Starting within 84 days of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Starting within 6 weeks of completion of surgery or radiation therapy (if indicated), patients without pathologic complete response (pCR) receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET/CT on study, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

After completion of study treatment, patients are followed up at 1, 6, and 12 months post-surgery then every 3 months for 2 years, every 6 months in year 3, and then annually thereafter.

Objective
PRIMARY OBJECTIVE:

I. To determine if neoadjuvant immunotherapy combined with response-adapted oncologic surgery improves site-reported event-free survival (EFS) compared to standard-of-care surgery in resectable stage III/IV cutaneous squamous cell carcinoma (CSCC).

SECONDARY OBJECTIVES:

I. To compare disease-free survival (DFS) between arms. II. To compare overall survival (OS) between arms. III. To compare adverse events (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) between arms.

IV. To assess pathologic complete response in arm 2.

Treatment This phase III trial compares the effect of adding cemiplimab to standard therapy (surgery with or without radiation) versus standard therapy alone in treating patients with stage III/IV squamous cell skin cancer that is able to be removed by surgery (resectable) and that may have come back after a period of improvement (recurrent). The usual treatment for patients with resectable squamous cell skin cancer is the removal of the cancerous tissue (surgery) with or without radiation, which uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cemiplimab has been approved for the treatment of skin cancer that has spread or that cannot be removed by surgery, but it has not been approved for the treatment of skin cancer than can be removed by surgery.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Melanoma/Skin cancer

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital