C-POST Protocol Update: A Phase 3, Randomized, Double-Blind Study of Adjuvant Cemiplimab vs. Placebo Post Surgery and Radiation Therapy in Patients with High-Risk Cutaneous Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with an incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is >95%, some patients have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment. Postoperative radiation therapy (RT) is recommended for these patients, but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk CSCC. Here, we provide a summary of the most recent study protocol amendment. <h3>Materials/Methods</h3> C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for patients with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50 Gy, within 10 weeks before randomization) (NCT03969004). Patients with at least one of the following high-risk features are eligible: (1) nodal disease with (a) extracapsular extension and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of extracapsular extension; (2) in-transit metastases; (3) T4 lesion; (4) perineural invasion; and (5) recurrent CSCC with at least one other risk factor. Patients with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), patients are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), patients in the placebo arm who experience disease recurrence and patients in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab 350 mg Q3W for up to 96 weeks. The trial is expected to enroll 412 patients from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival; secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic. <h3>Results</h3> Not applicable (trial in progress) <h3>Conclusion</h3> Not applicable (trial in progress)