A Phase 2 Study of Neoadjuvant Cemiplimab for Stage II to IV (M0) Cutaneous Squamous Cell Carcinoma (CSCC)

The primary objective of this Phase 2 study is to evaluate the efficacy of **neoadjuvant cemiplimab** in patients with Stage II to IV (M0) cutaneous squamous cell carcinoma, as measured by the pathologic complete response (pCR) rate per independent central pathology review. This objective is clinically relevant as achieving a high pCR rate can indicate a significant reduction in tumor burden prior to surgical intervention, potentially improving surgical outcomes and long-term prognosis.

Secondary objectives include:

• Evaluating the efficacy of neoadjuvant cemiplimab on measures of disease response, including major pathologic response (mPR) rate per independent central pathology review, pCR rate and mPR rate per local pathology review, and overall response rate (ORR) prior to surgery according to local assessment using RECIST 1.1.
• Assessing the efficacy of neoadjuvant cemiplimab on event-free survival (EFS), disease-free survival (DFS), and overall survival (OS).
• Evaluating the safety profile of neoadjuvant cemiplimab.
• Assessing changes in the surgical plan (ablative and reconstructive procedures) from the screening period to definitive surgery, according to both investigator review and independent surgical expert review.
• Assessing changes in the post-surgical management plan (radiation, chemoradiation, or observation) from the screening period to post-surgery pathology review, according to both investigator review and independent surgical expert review.

The clinical trial involves participants diagnosed with **Stage II to IV cutaneous squamous cell carcinoma**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on their diagnosis of Stage II to IV (M0) cutaneous squamous cell carcinoma, with the requirement that surgery would be recommended in routine clinical practice. For Stage II patients, the lesion must be at least 3 cm at the longest diameter. All participants must have at least one lesion measurable by RECIST 1.1 and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The trial includes individuals with adequate organ, bone marrow, and hepatic function. Both vulnerable and non-vulnerable populations are included in the study. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **cemiplimab** as a neoadjuvant treatment for patients with Stage II to IV (M0) cutaneous squamous cell carcinoma (CSCC). This is a Phase 2, randomized, double-blind, controlled study. The primary objective is to assess the pathologic complete response (pCR) rate through independent central pathology review. Secondary endpoints include major pathologic response (mPR) rate, objective response rate (ORR) prior to surgery, event-free survival (EFS), disease-free survival (DFS), overall survival (OS), and the incidence of adverse events (AEs) and serious adverse events (SAEs).

The trial is expected to last until September 2025, with recruitment having commenced in October 2022. Participants will be involved in the study for a maximum treatment period of 60 days, receiving **cemiplimab** via intravenous infusion. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as measurable lesions by RECIST 1.1 and adequate organ function, followed by treatment visits where the investigational product is administered, and regular follow-up visits to monitor response and safety. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it in the participant's best interest. The study is not categorized as low intervention, and it adheres to the guidelines set forth by the European Medicines Agency (EMA) for a Phase 2 trial. The investigational product, LIBTAYO 350 mg concentrate for solution for infusion, is not a pediatric formulation and is administered solely through intravenous infusion. The trial aims to provide valuable insights into the potential benefits of **cemiplimab** in treating advanced CSCC, with a focus on improving surgical and post-surgical outcomes.

The clinical trial involves the administration of **LIBTAYO**, a **350 mg concentrate for solution for infusion**. The active substance in this experimental medication is **cemiplimab**, a protein-based therapeutic agent. The pharmaceutical form of LIBTAYO is a concentrate that requires preparation into a solution for intravenous infusion. The administration route is exclusively through **intravenous infusion**, ensuring direct delivery into the bloodstream. The dosing regimen specifies a maximum daily dose of 16.67 mg, with a cumulative maximum total dose of 7000 mg over the treatment period. The maximum treatment duration is set at 60 days. The product is manufactured by Regeneron Ireland D.A.C. and is not formulated for pediatric use. The trial aims to evaluate the efficacy of neoadjuvant cemiplimab in patients with Stage II to IV (M0) cutaneous squamous cell carcinoma (CSCC).

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the administration of the experimental drug, LIBTAYO. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol and to accurately assess the therapeutic outcomes of cemiplimab. The trial's primary objective is to measure the efficacy of cemiplimab by evaluating the pathological complete response (pCR) rate as determined by an independent central pathology review.

The efficacy of neoadjuvant **cemiplimab** in the treatment of Stage II to IV (M0) Cutaneous Squamous Cell Carcinoma (CSCC) will be assessed primarily through the pathologic complete response (pCR) rate. This primary endpoint will be evaluated by an independent central pathology review. Secondary endpoints include the major pathologic response (mPR) rate, both assessed by independent central and local pathology reviews, and the objective response rate (ORR) prior to surgery, according to investigator assessment using RECIST 1.1. Additional secondary endpoints encompass event-free survival (EFS), disease-free survival (DFS), overall survival (OS), and various safety parameters such as the incidence of adverse events (AEs), serious adverse events (SAEs), deaths, and laboratory abnormalities. Changes in surgical and post-surgical management plans will also be evaluated.