Cemiplimab Moves Closer to EU Approval in Adjuvant CSCC

Regeneron Pharmaceuticals’ PD-1 inhibitor Libtayo (cemiplimab) has taken another significant step toward reshaping the treatment landscape for cutaneous squamous cell carcinoma (CSCC). Following its US FDA approval earlier this month, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has now issued a positive opinion recommending cemiplimab as an adjuvant treatment for adults with CSCC at high risk of recurrence after surgery and radiation. A final decision from the European Commission is expected within months.^1-2

This marks a pivotal moment for clinicians managing high-risk CSCC, an aggressive subset of non-melanoma skin cancer (NMSC) that, despite curative-intent surgery and radiotherapy, remains prone to recurrence and metastasis.

Defining a New Standard

The CHMP’s positive opinion is underpinned by robust results from the phase 3 C-POST trial (NCT03969004), a global, randomized, double-blind study comparing adjuvant cemiplimab with placebo in 415 patients who had completed surgery and postoperative radiation but remained at high risk of recurrence due to adverse pathological features.

At a median follow-up of 24 months, cemiplimab demonstrated a 68% reduction in the risk of disease recurrence or death compared with placebo (HR 0.32; 95% CI, 0.20–0.51; p<0.0001). The 24-month disease-free survival (DFS) was 87.1% in the cemiplimab arm versus 64.1% with placebo, as reported in the New England Journal of Medicine. Rates of locoregional and distant recurrence were also substantially lower in the treatment group (4% vs. 17% and 5% vs. 13%, respectively).³

Vishal A. Patel, MD, associate professor of dermatology at George Washington University, emphasized the clinical significance of these findings in a previous news release:

“Patients whose CSCC is at a high risk of recurrence following surgery and radiation often have the poorest outcomes. Until now, we lacked options to help prevent a devastating recurrence.”

Safety and Tolerability Profile

The safety profile of cemiplimab in the adjuvant CSCC setting aligned with prior experience in advanced cutaneous malignancies. Treatment-emergent adverse events (AEs) occurred in 91% of patients receiving cemiplimab and 89% receiving placebo. Grade ≥3 AEs were reported in 24% and 14% of patients, respectively.

The most frequent AEs (≥10%) included fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism, and maculopapular rash. Hypertension was the only grade ≥3 AE occurring in more than 2% of patients in the cemiplimab arm. Treatment discontinuations due to AEs occurred in 10% of the cemiplimab group and 2% of the placebo group.

Notably, the safety consistency across trials reinforces cemiplimab’s manageability in both advanced and adjuvant contexts.

Expanding the Role of PD-1 Blockade

With 5 FDA-approved indications, cemiplimab is increasingly recognized as a versatile PD-1 inhibitor with activity across several solid tumors. It functions by blocking the PD-1 receptor on T cells, thereby restoring antitumor immune activity that cancer cells often suppress.

Israel Lowy, MD, PhD, head of oncology clinical development at Regeneron, commented on the drug’s growing impact:

“The FDA approval of cemiplimab as the first and only immunotherapy for adjuvant treatment of CSCC with a high risk of recurrence after surgery and radiation is a pivotal moment for patients battling this disease.”

Regeneron’s proprietary VelocImmune® technology underpins cemiplimab’s development, and the company continues to evaluate its efficacy both as monotherapy and in combination with other agents across diverse tumor types.

Clinical and Epidemiological Relevance

CSCC is the second most common form of skin cancer worldwide, with incidence rates rising sharply, particularly among aging populations with cumulative UV exposure. In Europe, non-melanoma skin cancers are projected to increase by 40% by 2040, emphasizing the growing need for effective preventive and adjuvant therapies.

While early-stage CSCC is often curable with surgery, patients with nodal involvement, perineural invasion, or locally recurrent disease face substantially worse outcomes. Until the advent of adjuvant immunotherapy, these patients had no approved systemic options to mitigate recurrence risk.

Looking Ahead

Pending formal European Commission approval, cemiplimab could soon become the first immunotherapy authorized in the EU for adjuvant treatment of CSCC at high risk of recurrence, a milestone expected to redefine standard care for this challenging subset of patients.

As George D. Yancopoulos, MD, PhD, Regeneron’s chief scientific officer, noted in the release,

“This approval provides patients with CSCC at high risk of disease recurrence following surgery and radiation a much-needed option.”

If adopted across Europe, cemiplimab’s adjuvant indication may shift the therapeutic paradigm toward earlier immunologic intervention, aiming not merely to treat advanced disease but to prevent its recurrence altogether.

References

1. Libtayo® (cemiplimab) recommended for EU approval by the CHMP for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence after surgery and radiation. News release. Regeneron Pharmaceuticals. Published October 17, 2025. Accessed October 17, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-recommended-eu-approval-chmp-adjuvant

2. Libtayo® (cemiplimab-rwlc) Approved in the U.S. as First and Only Immunotherapy for Adjuvant Treatment of Cutaneous Squamous Cell Carcinoma (CSCC) with a High Risk of Recurrence After Surgery and Radiation. News release. Regeneron Pharmaceuticals. Published October 8, 2025. Accessed October 17, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only

3. Rischin D, Porceddu S, Day F, et al. Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2025;393(8):774-785. doi:10.1056/NEJMoa2502449