Evaluation of Neoadjuvant Cemiplimab and Imiquimod with Laser Therapy in High-Risk Resectable Cutaneous Basal Cell Carcinoma

The primary objective of this study is to assess the **safety** and toxicity of the combination of intravenous **cemiplimab** plus topical **imiquimod** (with fractional laser therapy) as a neoadjuvant treatment in patients with high-risk and potentially resectable **cutaneous basal cell carcinoma** (BCC) during the Phase Ib part of the trial. This evaluation is crucial for determining the treatment's viability and potential adverse effects in this patient population. For the Phase II part, the primary objective is to evaluate the antitumoral activity in terms of the 3-year rate of relapse-free survival (RFS) according to RECIST 1.1 criteria, using intravenous cemiplimab alone or in combination with topical imiquimod (plus fractional laser therapy) as a neoadjuvant treatment. This objective is clinically relevant as it aims to establish the long-term efficacy of the treatment in preventing cancer recurrence.

Secondary objectives include:

• Evaluating the pathological complete response rate (pCR) according to Immune-Related Pathologic Response Criteria (irPRC) as a surrogate of efficacy at short follow-up in both Phase Ib and Phase II.
• Assessing the activity in terms of response rate (RECIST 1.1), duration of response, clinical benefit, relapse-free survival/progression-free survival (RFS/PFS), and overall survival (OS).
• Determining the rate of resectability (downstaging) of BCC after 4 cycles of treatment.
• Evaluating the safety of the intended treatment regimen based on the frequency and severity of adverse events and treatment-related adverse events (TRAEs) assessed by NCI CTCAE v5.0.

The clinical trial involves participants diagnosed with **Cutaneous Basal Cell Carcinoma** (BCC), focusing on those with high-risk and potentially resectable tumors. The study population includes both male and female adults aged 18 years and older. Participants are required to have a histologically confirmed diagnosis of BCC, with tumors that are potentially resectable with curative intent. The trial does not include vulnerable populations. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Lifestyle considerations such as diet and physical activity are not detailed in the available data. Key inclusion criteria include having at least one measurable lesion by RECIST v1.1 and a life expectancy of at least 24 weeks. Participants must also have adequate organ and marrow function. The selection process for the trial population is not explicitly described in the provided data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of a combination therapy involving **cemiplimab** and **imiquimod** in patients with high-risk, potentially resectable **cutaneous basal cell carcinoma**. This trial is structured as a Phase Ib/II study, incorporating a randomized, double-blind, controlled methodology to ensure robust and unbiased results. The trial is expected to commence recruitment on July 1, 2025, and conclude by January 1, 2030, with the overall duration spanning approximately five years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and health status. Following successful screening, participants will be randomized to receive either the investigational treatment or a control. The treatment phase will include regular follow-up visits to monitor **adverse events** and assess treatment response using criteria such as RECIST 1.1. The end-of-study visit will occur after the final treatment cycle, where comprehensive evaluations will be conducted to determine the primary and secondary endpoints, including **relapse-free survival** and **overall survival**.

Participant involvement is anticipated to last for the duration of the treatment phase, with additional follow-up extending up to three years post-treatment to assess long-term outcomes. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, withdrawal of consent, or any situation where continued participation is deemed unsafe by the investigator. The trial aims to provide valuable insights into the potential benefits of combining **cemiplimab** and **imiquimod** as a neoadjuvant treatment for this patient population.

The clinical trial involves the administration of **LIBTAYO**, a **350 mg concentrate for solution for infusion**. The active substance in LIBTAYO is **cemiplimab**, a protein-based therapeutic agent. This medication is administered via **intravenous infusion**. The frequency and specific dosing schedule are determined by the study protocol, ensuring adherence to safety and efficacy standards. Participant compliance is monitored through regular assessments and documentation of infusion sessions.

In addition to LIBTAYO, the trial includes the use of **IMUNOCARE 5% crema**, which contains the active substance **imiquimod**, a chemical compound. This medication is applied **topically** as a cream. The application schedule is outlined in the study protocol, with participant adherence monitored through self-reporting and periodic evaluations by the study team. The combination of these treatments aims to assess their safety and efficacy as a neoadjuvant therapy in patients with high-risk cutaneous basal cell carcinoma.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. For the Phase Ib portion, the primary endpoint is the incidence of adverse events (AEs) and treatment-related adverse events (TRAEs) as evaluated by the NCI CTCAE v5.0. In Phase II, the primary endpoint is the **relapse-free survival (RFS)** rate at 3 years, defined as the proportion of patients free from locoregional progression, recurrence, distant metastasis, or death from any cause, measured from the date of study treatment initiation.

Secondary endpoints for Phase Ib include the pathological response assessment, which measures the proportion of patients achieving a pathologic complete response (pCR) according to the Immune-Related Pathologic Response Criteria (irPRC), with 0% residual viable tumor in post-therapy specimens. Additional secondary endpoints include objective response rate (ORR), clinical benefit rate (CBR), duration of clinical benefit (DBC), RFS, and overall survival (OS). For Phase II, secondary endpoints encompass pCR, ORR, CBR, DBC, rate of resectability, downstaging, OS, AEs, and TRAEs.