EC Approves Adjuvant Cemiplimab in CSCC at High-Risk of Recurrence

The European Commission has approved adjuvant cemiplimab-rwlc (Libtayo) as treatment for adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence following surgery and radiation, according to a press release from the developer, Regeneron Pharmaceuticals.¹

The approval expands the EU indication for cemiplimab in advanced CSCC to now include patients at high risk of disease recurrence. Additionally, this approval follows the FDA approval of cemiplimab in the same indication, which occurred in October 2025.²

Both approvals were supported by data from the landmark, phase 3 C-POST trial (NCT03969004), which evaluated the disease-free survival (DFS) of patients with high-risk CSCC who were treated with cemiplimab compared with those treated with placebo. Most recently, results from the trial were published in the New England Journal of Medicine.³

In C-POST, the median potential follow-up from randomization to the data-cutoff date was 24 months (range, 2-64). Cemiplimab treatment significantly improved DFS vs placebo, with 24 events vs 65 events (HR, 0.32; 95% CI, 0.20-0.51; P <.001). The estimated 24-month DFS was 87.1% (95% CI, 80.3%-91.6%) compared with 64.1% (95% CI, 55.9%-71.1%), respectively.

Across all prespecified subgroups, a DFS benefit with cemiplimab vs placebo was observed. Among them were patients from North America (HR, 0.18; 95% CI, 0.05-0.63), patients with high-risk category nonmodal status (HR, 0.27; 95% CI, 0.13-0.56), and patients with a PD-L1 tumor proportion score of 1% or higher (HR, 0.28; 95% CI, 0.15-0.52).

The estimated locoregional recurrence-free rate at 24 months was 94.6% (95% CI, 89.1%-97.3%) with cemiplimab compared with 76.7% (95% CI, 69.1%-82.6%) in the placebo group, with locoregional recurrence occurring in 9 and 40 patients, respectively (HR, 0.20; 95% CI, 0.09-0.40). The estimated distant recurrence-free rate at 24 months was 94.3% (95% CI, 89.0%-97.1%) with cemiplimab vs 83.8% (95% CI, 76.3%-89.0%) with placebo; distant recurrence occurred in 10 and 26 patients (HR, 0.35; 95% CI, 0.17-0.72).

Of the 46 patients who began the study on placebo but received cemiplimab for recurrence, 43% had an objective radiographic response.

The 2-year overall survival (OS) was 94.8% (95% CI, 89.6%-97.4%) with cemiplimab vs 92.3% (95% CI, 86.5%-95.7%) with placebo (HR, 0.86; 95% CI, 0.39-1.90); as of the data-cutoff date of April 7, 2025, 33 deaths had occurred, including 15 patients in the cemiplimab arm and 18 patients in the placebo arm (HR, 0.78; 95% CI, 0.39-1.56).

“While CSCC can often be treated successfully with surgery and radiation, some patients face the persistent threat of disease recurrence and potentially fatal outcomes. This highlights a critical need for earlier intervention, but immunotherapy has until now been reserved just for advanced cases,” stated Paolo Bossi, MD, head of the Head and Neck Medical Oncology Unit and associate professor of Medical Oncology at Humanitas University and Humanitas Cancer Center in Milan, Italy, in the press release.¹ “As the only immunotherapy shown to improve DFS in this setting, [cemiplimab] could change the outlook for these earlier-stage patients in need.”

A total of 415 patients with CSCC at high risk of recurrence were randomly assigned to receive either adjuvant cemiplimab (n = 209) or placebo (n = 206). Originally, treatment consisted of cemiplimab at 350 mg or placebo administered intravenously, every 3 weeks; however, a protocol amendment altered treatment to be cemiplimab intravenously at 350 mg every 3 weeks for 12 weeks, followed by cemiplimab at 700 mg every 6 weeks for an additional 36 weeks, or placebo every 3 weeks for 12 weeks, followed by placebo every 6 weeks for an additional 36 weeks. In part 2 of the trial, patients who experienced disease recurrence in either group had the option to receive subsequent cemiplimab.

Eligible patients were 18 years or older with local or regional CSCC and had completed curative-intent surgery, with macroscopic gross resection of all disease, and postoperative radiotherapy at a biologically equivalent dose of at least 50 Gy within 2 to 10 weeks of random assignment.

The primary end point of the trial was DFS. Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, OS, second primary CSCC tumors, and safety.

Regarding safety, any-grade, any-cause adverse events (AEs) occurred in 91.2% of the cemiplimab group and 89.2% of the placebo group. The most common AEs in the respective groups were fatigue (22.0% vs 21.6%), pruritus (16.1% vs 12.3%), rash (16.1% vs 8.8%), and diarrhea (15.6% vs 18.6%). Any-cause AEs of grade 3 or higher occurred in 23.9% vs 14.2%, and AEs of grade 3 or higher believed to be related to treatment occurred in 9.8% of the cemiplimab group.

Any-grade immune-related AEs occurred in 22.9% of the cemiplimab group vs 6.4% of the placebo group, with 7.3% of the cemiplimab group experiencing an immune-related AE of grade 3 or higher vs 0% of the placebo group. Treatment was discontinued by 9.8% of the cemiplimab group and 1.5% of the placebo group.

“CSCC is one of the fastest-growing forms of skin cancer, and the approval of [cemiplimab] by the European Commission reflects a meaningful shift in how this disease could be treated in the adjuvant setting,” George D. Yancopoulos, MD, PhD, board co-chair, president, and chief scientific officer of Regeneron, said in the release.¹ “Building on our existing indication in advanced CSCC, this is the sixth approval for [cemiplimab] in the EU and underscores our commitment to delivering innovative treatments across cancers where patients continue to face some of the greatest gaps in care.”

References

1. Libtayo® (cemiplimab) approved in the European Union as first and only immunotherapy for adjuvant treatment of cutaneous squamous cell carcinoma (CSCC) with high risk of recurrence after surgery and radiation. News release. Regeneron Pharmaceuticals. November 19, 2025. Accessed November 19, 2025. https://tinyurl.com/4nhn8z7a
2. FDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed November 19, 2025. https://tinyurl.com/2z7bkjyn
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