Breaking Ground in Skin Cancer: Phase 3 C-POST Trial Demonstrates Significant Clinical Benefits of Libtayo in High-Risk Cutaneous Squamous Cell Carcinoma Advances

A recent Phase 3 clinical trial, known as C-POST, has demonstrated that adjuvant treatment with Libtayo (cemiplimab) significantly improves disease-free survival (DFS) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery. These findings position Libtayo as the first and only immunotherapy to show a statistically significant and clinically meaningful benefit in this patient population in the adjuvant setting. Libtayo is a fully human monoclonal antibody that targets the immune checkpoint receptor programmed cell death protein-1 (PD-1) on T-cells, thereby inhibiting the PD-1 pathway and enhancing the immune system's ability to combat cancer cells. In the United States, Libtayo is approved for treating patients with advanced stages of CSCC that cannot be cured with surgery or radiation, patients with advanced stages of basal cell carcinoma (BCC) that cannot be cured with surgery and have been previously treated with hedgehog inhibitors, and patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). 

The C-POST trial enrolled 415 patients with high-risk CSCC who had undergone surgery. Participants were randomized to receive either Libtayo or a placebo for up to 48 weeks. The primary endpoint was DFS, which was specified as the time from randomization to the first documented disease recurrence or death from any cause. At the first interim analysis, which had a median follow-up time of 24 months, Libtayo displayed a 68% reduction in the risk of disease recurrence or death compared to placebo (hazard ratio: 0.32; 95% confidence interval: 0.20-0.51; p<0.0001). Adverse events (AEs) were monitored in both the Libtayo and placebo groups. AEs of any grade occurred in 91% of patients receiving Libtayo and 89% of those on placebo. Grade ≥3 AEs were reported in 24% of the Libtayo group compared to 14% in the placebo group. Treatment discontinuations due to adverse reactions occurred in 10% of patients on Libtayo and 1.5% on placebo. Additionally, two patients in each group experienced an AE leading to death.  

“At the first prespecified interim analysis, Libtayo achieved a remarkably high bar in improving disease-free survival. These landmark results demonstrate Libtayo could represent a major advance in delaying recurrence in these vulnerable patients.” said Dr Danny Rischin, lead investigator and head of the department of medical oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia. These results suggest that Libtayo may represent a major advance in delaying recurrence for patients with high-risk CSCC, for whom there are currently no approved adjuvant treatment options.  

The C-POST trial will continue for additional follow-up, including analysis of overall survival. Detailed results are expected to be presented at an upcoming medical meeting, and regulatory submissions are planned for the first half of 2025. These findings underscore the potential of Libtayo to address unmet needs in high-risk CSCC, offering hope for improved patient outcomes in this challenging setting. 

Reference: 

Adjuvant Libtayo (cemiplimab) significantly improves disease-free survival (DFS) after surgery in high-risk cutaneous squamous cell carcinoma CSCC) in phase 3 trial. News Release. Regeneron. January 13, 2025. Accessed March 20, 2025. https://investor.regeneron.com/news-releases/news-release-details/adjuvant-libtayor-cemiplimab-significantly-improves-disease-free