High-Risk CSCC Trial Validates Cemiplimab's Potential

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Regeneron Pharmaceuticals reported results this week from the phase 3 C-POST trial, which investigated the efficacy and safety of the PD-1 inhibitor cemiplimab (Libtayo) as adjuvant therapy in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery. In a news release, the company stated the trial results indicated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared to a placebo.¹

“While surgery is curative for most people living with cutaneous squamous cell carcinoma, many are burdened with a higher risk of recurrence that can lead to death or disfiguration,” said Danny Rischin, MD, MBBS, FRACP, Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and lead investigator of the trial, in the release. “At the first prespecified interim analysis, [cemiplimab] achieved a remarkably high bar in improving disease-free survival in high-risk cutaneous squamous cell carcinoma. With no currently approved options in the adjuvant setting, these landmark results demonstrate [cemiplimab] could represent a major advance in delaying recurrence in these vulnerable patients.”

Study Design and Objectives 

The C-POST trial is a global, randomized, double-blind, placebo-controlled phase 3 study designed to evaluate the impact of cemiplimab on DFS in patients with high-risk CSCC. Participants included 415 individuals who had completed surgery and post-operative radiation therapy. Patients were randomized to receive cemiplimab or placebo for up to 48 weeks. The primary endpoint was DFS, defined as the time from randomization to the first documented recurrence.

Key Findings

At the first interim analysis, conducted with a median follow-up of 24 months, the release stated cemiplimab demonstrated a 68% reduction in the risk of disease recurrence compared to the placebo group (hazard ratio: 0.32; 95% CI: 0.20–0.51; p<0.0001). These findings suggest that cemiplimab could delay recurrence in patients with high-risk CSCC.

Researchers found that safety profile of cemiplimab was consistent with prior studies. Adverse events (AEs) of any grade were reported in 91% of patients in the cemiplimab arm and 89% in the placebo arm. The study stated grade 3 or higher AEs were observed in 24% of patients treated with cemiplimab compared to 14% in the placebo group. Treatment discontinuations due to adverse reactions occurred in 10% of the cemiplimab group versus 1.5% in the placebo group, according to the study. Deaths related to adverse events were reported in 2 patients from each group.

Implications and Future Directions

Cemiplimab is currently approved for certain advanced skin cancers, including advanced CSCC, but no therapies are specifically approved for the adjuvant treatment of resected high-risk CSCC.² Researchers stated the C-POST trial findings suggest cemiplimab may represent a therapeutic option for reducing the risk of recurrence in this setting. However, the trial will continue to collect data on overall survival and other secondary endpoints, and the results will inform potential regulatory submissions in 2025.

“Regeneron has long been a pioneer in non-melanoma skin cancer research. [Cemiplimab] was the first PD-1 inhibitor approved for certain patients with advanced cutaneous squamous cell carcinoma and has become a standard of care in this setting,” said Israel Lowy, MD, PhD, Clinical Development Unit Head, Oncology, at Regeneron, in the news release. “With these results, [cemiplimab] now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma with adjuvant treatment. This trial is a testament to our unrelenting commitment to investigating areas where patient need remains high and to pursuing clinical research across diverse stages of skin cancer.”

Considerations

While the trial demonstrated significant DFS benefits, the release statedthe increased incidence of severe adverse events and treatment discontinuations highlights the need for careful patient selection and monitoring. Detailed results will be presented at upcoming scientific meetings, and further analysis will provide insights into the long-term benefits and risks of cemiplimab in this population.

Conclusion

The C-POST trial provides evidence supporting the use of cemiplimab as an adjuvant therapy for high-risk CSCC, demonstrating improved DFS compared to placebo. The release stated that further research and regulatory evaluation will determine its role in clinical practice.

References

1. 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 Pharmaceuticals, Inc. Published January 13, 2025. Accessed January 14, 2025. https://investor.regeneron.com/news-releases/news-release-details/adjuvant-libtayor-cemiplimab-significantly-improves-disease-free
2. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. Updated January 18, 2019. Accessed January 14, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma#:~:text=On%20Sept.,curative%20surgery%20or%20curative%20radiation.