Trial in Progress: A Phase 3 Randomized Study of Low-Dose Intralesional Cemiplimab Versus Primary Surgery for Patients With Early-Stage Cutaneous Squamous Cell Carcinoma (CLEAR CSCC)

Introduction Cemiplimab 350 mg every 3 weeks intravenously is approved for the treatment of advanced cutaneous squamous cell carcinoma (CSCC) in patients who are not candidates for curative surgery or radiation. For early-stage CSCC, surgery is the standard of care. For patients for whom non-surgical management of early-stage CSCC is preferable, low-dose intralesional (IL) cemiplimab demonstrated promising clinical activity in a pilot study (NCT03889912). The primary objective of this study is to assess the non-inferiority of IL cemiplimab versus primary surgery by event-free survival. Secondary objectives include safety, tolerability, longest diameter of surgical defect after resection in both arms, and composite, complete response in the experimental arm. Trial design In this phase 3 randomized (NCT06585410), open-label, multicenter study, approximately 369 patients with early-stage CSCC will be randomized 2:1 to cemiplimab (5 mg IL every week for 6 weeks) versus primary surgery. Key inclusion criteria are: ≥18 years of age; histologically confirmed invasive CSCC target lesion that is ≥1.0–≤2.0 cm (longest diameter) located in the head and neck, hand, or pre-tibial surface; and adequate performance status and organ function. Key exclusion criteria include autoimmune disease, concurrent or prior solid tumor or hematologic malignancy (except for protocol-allowed exceptions), and a history of solid organ transplant. Patients will be followed for approximately 3 years. Results The study is actively recruiting. Enrollment is planned at study sites across North America and Australia. Conclusions This study will help establish the potential clinical utility and broader applicability of low-dose IL cemiplimab in early-stage CSCC.