FDA Approves Libtayo® (cemiplimab-rwlc) for Adjuvant Treatment of High-Risk Cutaneous Squamous Cell Carcinoma: Clinical Evidence and Expert Insights

On October 8, 2025, the U.S. Food and Drug Administration (FDA) granted approval to cemiplimab-rwlc, marketed as Libtayo® by Regeneron Pharmaceuticals, for the adjuvant treatment of adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence following surgery and radiation therapy. This approval establishes Libtayo as the first and only immunotherapy approved in this setting, marking a pivotal advancement in the management of high-risk CSCC and offering a new standard of care to prevent disease recurrence.​

Libtayo® (cemiplimab-rwlc) is developed and commercialized by Regeneron Pharmaceuticals, Inc., The drug was developed using Regeneron’s proprietary VelocImmune® technology, which enables the generation of fully human monoclonal antibodies.

About the Drug: Libtayo (cemiplimab-rwlc)

Libtayo is a fully human monoclonal antibody that targets the programmed death receptor-1 (PD-1) on T cells. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, Libtayo reactivates the immune system’s ability to detect and destroy cancer cells. It is administered intravenously and is approved under the nonproprietary name cemiplimab-rwlc in the U.S. outside the U.S., it is known simply as cemiplimab.​

Libtayo® (cemiplimab-rwlc) was first approved by the FDA in September 2018 for patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who were not candidates for curative surgery or radiation. Since then, it has gained approval for five different indications across several cancer types, including the recent adjuvant therapy approval for high-risk CSCC, further establishing its role as a key immunotherapy option in oncology.

About the Disease: Cutaneous Squamous Cell Carcinoma (CSCC)

Cutaneous squamous cell carcinoma is the second most common form of skin cancer, with approximately 1.8 million cases diagnosed annually in the United States alone. While localized CSCC is typically curable with surgical excision and radiation, patients with high-risk features face a significant risk of recurrence and metastasis. High-risk factors include tumor diameter >2 cm, poor differentiation, perineural invasion, nodal involvement, extracapsular extension, and location on high-risk sites such as the ear, lip, or temple.​

Metastatic CSCC carries a poor prognosis, with 5-year survival rates dropping to 25–40% in cases with nodal metastasis and as low as 10% in those with distant spread. Despite the high incidence of CSCC, there were previously no FDA-approved systemic therapies for adjuvant use after surgery and radiation, creating a critical unmet need.​

Clinical Evidence: The C-POST Trial

The approval was based on the pivotal Phase III C-POST trial (NCT03969004), a randomized, double-blind, placebo-controlled study involving 415 patients with high-risk CSCC who had undergone complete surgical resection and completed adjuvant radiation therapy within two to 10 weeks of randomization. Patients were randomized 1:1 to receive either cemiplimab-rwlc or placebo.​ The primary endpoint was disease-free survival (DFS), defined as the time from randomization to the first documented recurrence or death from any cause. Key secondary endpoints included loco regional recurrence-free survival, distant recurrence-free survival, overall survival (OS), and safety.​

Results

Libtayo demonstrated a statistically significant and clinically meaningful improvement in DFS. The hazard ratio for recurrence or death was 0.32 representing a 68% reduction in risk means (Patients taking Libtayo experienced 68% less risk of cancer recurrence or death during the study period than those on placebo) Median DFS was not reached in the Libtayo arm (This indicates that more than half of the patients treated with Libtayo were still alive without cancer recurrence when the data were analyzed, so the exact middle point couldn’t be determined yet) versus 49.4 months in the placebo arm. At two years, DFS was 87% with Libtayo (87 out of 100 patients taking Libtayo had no sign of cancer returning) compared to 64% with placebo.​

Libtayo also reduced the risk of locoregional recurrence by 80% and distant recurrence by 65%. These results were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine, underscoring their clinical significance.​

Safety Profile

The safety profile of Libtayo in the adjuvant setting was consistent with its established profile in advanced cancers. Adverse events of any grade occurred in 91% of patients receiving Libtayo and 89% in the placebo group. The most common adverse reactions were rash, pruritus, fatigue, diarrhea and hypothyroidism.​

Serious adverse events occurred in 18% of patients, including pneumonia (1.5%), rash (1.5%), diarrhea (1.5%), adrenal insufficiency (1%), and arrhythmia (1%). Immune-mediated adverse reactions, infusion-related reactions, and complications of allogeneic hematopoietic stem cell transplantation are included in the prescribing information, necessitating vigilant monitoring.​

Key Opinions

Dr. George D. Yancopoulos, President and Chief Scientific Officer of Regeneron, stated: “This approval provides patients with CSCC at high risk of disease recurrence a much-needed option, as Libtayo is the only immunotherapy to demonstrate efficacy in this setting”.​

Samantha R. Guild, President of the AIM at Skin Cancer Foundation, added: “This approval is excellent news for those living with CSCC, and we applaud Regeneron for its commitment to addressing the needs of non-melanoma skin cancer through innovative research”.​

Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., research lead of the Phase 3 C-POST trial and Head of Neck Cancer and Cutaneous SCC at the Peter MacCallum Cancer Centre in Melbourne, Australia, emphasized the significance of the results: “The Phase 3 C-POST trial demonstrates that cemiplimab is a highly active therapy in high-risk CSCC, with clinically meaningful outcomes across primary and secondary endpoints and exceptionally low rates of locoregional and distant recurrence.”

From the industry perspective, Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology at Regeneron, stated: “Libtayo is the first medicine to demonstrate a statistically significant benefit in patients who have high-risk features for recurrence after resection of cutaneous squamous cell carcinoma and has the potential to become a new standard of care in the adjuvant setting.”

Implications of Approval

This approval redefines the treatment paradigm for high-risk CSCC, shifting from surgery and radiation alone to a multimodal approach incorporating immunotherapy. With no prior approved adjuvant therapies, Libtayo fills a critical gap and may become the new standard of care. The success of Libtayo in the adjuvant setting also strengthens its position as a versatile PD-1 inhibitor, now with five FDA-approved indications.​

Regeneron has also submitted a regulatory application to the European Medicines Agency, with a decision expected in the first half of 2026.

The FDA’s approval of Libtayo® for adjuvant use in high-risk cutaneous squamous cell carcinoma represents a landmark achievement in dermatologic oncology. Supported by robust clinical evidence from the C-POST trial, this approval offers a powerful new tool to improve disease-free survival and reduce recurrence in a patient population with historically poor outcomes. As the first and only immunotherapy approved in this setting, Libtayo sets a new benchmark in the fight against CSCC.