Regeneron’s Libtayo showed sustained disease-free survival benefit at 44 months in the Phase 3 C-POST trial, while overall survival findings remain inconclusive.
Written By: Aasritha Thippavajjala,, PharmD
Reviewed By: Pharmacally Editorial Team
Regeneron Pharmaceuticals announced longer-term findings from the Phase 3 C-POST trial evaluating Libtayo® (cemiplimab) as adjuvant treatment for adults with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery and postoperative radiotherapy. The findings were presented during a rapid oral session at the European Society for Medical Oncology (ESMO) Congress 2026 on October 25.
At a median follow-up of 44 months, the updated analysis reported an overall survival (OS) hazard ratio (HR) of 0.63 (95% CI, 0.36–1.11), corresponding to a 37% lower estimated hazard of death with cemiplimab compared with placebo. However, the confidence interval included 1.0, meaning the analysis has not established a statistically significant OS benefit. The update also reported sustained disease-free survival (DFS) benefit and exploratory findings from baseline circulating tumour DNA (ctDNA) analyses.
Trial Design and Patient Population
C-POST (NCT03969004) was a global, multicentre, randomised, double-blind, placebo-controlled Phase 3 trial involving 415 patients with CSCC at high risk of recurrence following surgery and postoperative radiotherapy. Patients were randomised to receive intravenous cemiplimab (n=209) or placebo (n=206) for up to 48 weeks.
High-risk eligibility criteria included nodal disease with extracapsular extension and at least one involved lymph node measuring 20 mm or larger, or at least three involved lymph nodes. Non-nodal criteria included in-transit metastases, perineural invasion, T4 lesions with bone invasion, or locally recurrent tumours with at least one additional high-risk feature.
Patients assigned to cemiplimab received 350 mg intravenously every three weeks for the first 12 weeks, followed by 700 mg every six weeks for up to 36 weeks. DFS was the primary endpoint, while OS was a secondary endpoint.
Key Results
Primary Endpoint: Disease-Free Survival (DFS)
Regeneron reported sustained DFS benefit with adjuvant cemiplimab at a median follow-up of 44 months. However, the October 25 announcement did not provide an updated overall DFS HR, corresponding confidence interval or absolute DFS rates.
The longer-term findings build on the original C-POST analysis published in the New England Journal of Medicine, which demonstrated a statistically significant reduction in the risk of recurrence or death with cemiplimab (HR, 0.32; 95% CI, 0.20–0.51; P<0.001). Estimated 24-month DFS was 87.1% with cemiplimab compared with 64.1% with placebo. These results established the primary-endpoint benefit that the latest follow-up continues to support.
Secondary Endpoint: Overall Survival (OS)
The updated analysis reported a 37% lower estimated hazard of death with cemiplimab (HR, 0.63; 95% CI, 0.36–1.11). Earlier estimates showed a 14% lower hazard at 24 months (HR, 0.86; 95% CI, 0.39–1.90) and a 22% lower hazard at 30 months (HR, 0.78; 95% CI, 0.39–1.56).
Although the successive estimates increasingly favoured cemiplimab, all three confidence intervals included 1.0. The announcement did not provide an OS p-value.
An important consideration is that 61 of 69 placebo-assigned patients (88%) who experienced recurrence subsequently received cemiplimab. This crossover complicates interpretation of the longer-term survival comparison because many patients initially assigned to placebo later received active treatment. However, its independent effect on the OS estimate cannot be quantified from the available data.
Exploratory Biomarker Analysis: Circulating tumour DNA (ctDNA)
Baseline ctDNA data were available for 191 patients, including 93 receiving cemiplimab and 98 receiving placebo. The exploratory analysis reported DFS benefit across both baseline minimal residual disease (MRD) subgroups.
Patients who were MRD-negative had a DFS HR of 0.45 (95% CI, 0.22–0.95), while those who were MRD-positive had an HR of 0.24 (95% CI, 0.07–0.86). These findings indicate that the observed DFS benefit extended to patients with and without detectable ctDNA at baseline. However, the exploratory results do not establish ctDNA as a validated biomarker for selecting patients for adjuvant treatment.
Safety Endpoint
Treatment-emergent adverse events (TEAEs) of any grade occurred in 94% of patients receiving cemiplimab and 91% receiving placebo. Grade 3 or higher TEAEs occurred in 26% and 17%, respectively. Treatment discontinuations due to TEAEs were reported in 10% of the cemiplimab group and 3% of the placebo group. TEAEs leading to death occurred in 2% of patients in each group.
The safety findings remained consistent with previously reported data, although the higher incidence of severe TEAEs and treatment discontinuations with cemiplimab remains relevant when assessing its benefit-risk profile.
Clinical Interpretation
The longer-term C-POST findings provide additional follow-up supporting the DFS benefit of adjuvant cemiplimab in patients with high-risk CSCC following surgery and radiotherapy. The updated OS estimate increasingly favoured cemiplimab, but its confidence interval continued to cross 1.0, leaving the magnitude and statistical certainty of an overall survival benefit unresolved.
The high rate of subsequent cemiplimab treatment among placebo patients who experienced recurrence is an important consideration when interpreting the survival findings. Meanwhile, the exploratory ctDNA results suggest that the DFS benefit was observed regardless of baseline MRD status, although further validation is required before ctDNA can guide treatment selection.
Cemiplimab received US FDA approval for this adjuvant indication in October 2025, followed by European Commission approval in November 2025. The 44-month findings add longer-term evidence to its established role in high-risk CSCC, while further follow-up will be important to clarify the overall survival outcomes.
References
Regeneron Pharmaceuticals. Libtayo® (cemiplimab) Longer-Term Data Show Increasing and Clinically Meaningful Overall Survival Benefit with Adjuvant Treatment in High-Risk Cutaneous Squamous Cell Carcinoma (CSCC). October 25, 2026.
Rischin D, et al. Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma. New England Journal of Medicine. 2025;393:774–785, DOI: 10.1056/NEJMoa2502449
Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients with High-Risk Cutaneous Squamous Cell Carcinoma. ClinicalTrials.gov. NCT03969004.
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.