Phase II Open-Label Single-Arm Multicentre Study of Cemiplimab for Organ Preservation in Locally Advanced Cutaneous Squamous Cell Carcinoma (INCEPT)

Primary objective: to assess whether upfront cemiplimab can eliminate the need for local therapies, such as surgery, in patients with locally advanced cutaneous squamous cell carcinoma, thereby supporting an organ preservation strategy. Secondary objectives: – evaluate the effect of the regimen on overall and progression‑free survival endpoints; – determine activity through pathological response rates (pathologic response); – capture changes in health status using patient-reported outcomes at baseline, at the end of treatment, and three months post‑treatment; – explore alterations in post‑surgical management plans (radiation versus observation) based on multidisciplinary review; – identify prognostic and predictive biomarkers.

The trial enrolled adult individuals (≥ 18 years) of both sexes with an ECOG performance status of 0–1 and adequate organ function, as defined by specific hematologic, hepatic, and renal laboratory criteria. Participants were required to have a histologically confirmed diagnosis of cutaneous squamous cell carcinoma classified as AJCC stage II (≥ 3 cm), III, or IV (M0) and deemed difficult to manage surgically or with curative radiotherapy after multidisciplinary evaluation. Eligible subjects had measurable disease per iPERCIST, were not candidates for curative surgery or radiotherapy, and consented to use effective contraception or met pregnancy testing requirements for women of child‑bearing potential. The selection process required signed informed consent and confirmation of eligibility according to the summary of product characteristics for cemiplimab monotherapy. The sponsor did not provide information on the total number of participants.

The study is a Phase II, open‑label, single‑arm investigation evaluating upfront cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma. Eligible participants undergo a screening visit to confirm inclusion criteria, including histologic diagnosis, adequate organ function, and measurable disease by iPERCIST. After eligibility confirmation, patients receive intravenous infusion of 350 mg of the drug every three weeks for up to 12 months, with study visits scheduled at baseline, each treatment cycle, at treatment completion, and at three‑month intervals during follow‑up. The primary endpoint assesses the proportion of participants who avoid surgery at one year; secondary endpoints include event‑free survival, overall survival, objective response rate, and patient‑reported outcomes. Participant involvement spans approximately 12 months of therapy plus an additional observation period, totaling up to 24 months. Early termination may occur if disease progression, unacceptable adverse events, withdrawal of consent, loss to follow‑up, or investigator decision deem continuation inappropriate. Recruitment began in June 2026 and the study is planned to conclude in December 2033.

The investigational product is LIBTAYO 350 mg concentrate for solution for infusion, containing the monoclonal antibody cemiplimab. Each dose consists of 350 mg of active substance prepared as a concentrate for solution for infusion and administered by intravenous infusion. The infusion is performed in accordance with the study protocol, with dosing recorded for each administration to ensure adherence to the prescribed schedule.

No additional non‑experimental therapies, such as standard‑of‑care treatments, placebo, or comparator agents, are specified for this study. All drug administration events are documented, and participant compliance with the infusion schedule is monitored through source‑document verification and study visit assessments.

Efficacy assessment will focus on the proportion of patients who do not require surgery at one year in the intention‑to‑treat population as the primary endpoint. Secondary efficacy parameters include event‑free survival (EFS), relapse‑free survival (RFS), overall survival (OS), objective response rate evaluated according to iPERCIST criteria, the proportion of confirmed pathological complete response (pCR) obtained by biopsy or surgery, patient‑reported outcomes using the NCI‑PRO‑CTCAE instrument, and Decision Regret Scale scores.

Measurements will be performed at predefined timepoints: baseline, at the end of upfront cemiplimab treatment, three months after treatment completion, and one year after treatment. Surgical necessity will be recorded at the 12‑month visit. Time‑to‑event endpoints (EFS, RFS, OS) will be calculated from the date of diagnosis to the respective event. Radiologic response will be assessed using iPERCIST criteria on imaging studies performed at baseline and at each follow‑up visit. Biopsies or surgical specimens will be obtained when indicated to confirm pCR. The NCI‑PRO‑CTCAE questionnaire will be administered at baseline, end of treatment, and three months post‑treatment to capture symptom burden. The Decision Regret Scale will be completed at the end of treatment and at the one‑year follow‑up. Data will be analyzed using proportion estimates for the primary endpoint, Kaplan‑Meier methods for survival outcomes, and appropriate statistical comparisons between responder versus non‑responder groups and between locally treated versus non‑locally treated cohorts.

The study population consists of patients with cutaneous squamous cell carcinoma receiving cemiplimab 350 mg intravenously as a single‑arm, open‑label intervention.