FDA Approves Cemiplimab for Adjuvant Cutaneous Squamous Cell Carcinoma

The US FDA has approved the supplemental biologics license application (sBLA) for cemiplimab-rwlc (Libtayo) as adjuvant treatment in adults with high-risk cutaneous squamous cell carcinoma (CSCC).¹

The sBLA approval was based on an extensive review of data from the pivotal phase 3 C-POST study (NCT03969004) which demonstrated a statistically significant and clinically meaningful improvement in its primary end point of disease-free survival (DFS) since interim analysis data were initially shared in January 2025.^1,2 The updated findings, including additional data for DFS and positive secondary end point data, reinforce this favorable trend and were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine.^3–6

For the primary end point, cemiplimab was associated with a 68% reduction (HR, 0.32; 95% CI, 0.20–0.51; P <.0001) in the risk of recurrence or death compared with placebo.^2-4 Furthermore, the estimated 24-month DFS with cemiplimab was longer than that of the placebo at 87.1% (95% CI, 80.3%–91.6%) compared with 64.1% (95% CI, 55.9%–71.1%).

Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, and safety.³ Compared with the placebo, cemiplimab also achieved lower risks of locoregional recurrence (HR, 0.20; 95% CI, 0.09–0.40) and distant recurrence (HR, 0.35; 95% CI, 0.17–0.72), equating to 80% and 65% risk reductions, respectively.

In terms of safety, adverse events (AEs) of grade 3 or higher were seen in 24% of patients in the cemiplimab arm (n = 205) and 14% of patients in the placebo arm (n = 204), with the most common AEs in the cemiplimab arm being fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism, and maculopapular rash. Treatment discontinuation due to AEs occurred in 10% and 2% of the cemiplimab and placebo arms, respectively; 2 patients experienced an AE leading to death.

"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 and immunotherapy was only available for patients with advanced CSCC who were no longer candidates for curative surgery or curative radiation,” Vishal A. Patel, MD, associate professor of Dermatology and of Medicine (Hematology/Oncology), George Washington University School of Medicine & Health Sciences and Director, Cutaneous Oncology Program, GW Cancer Center, stated in a press release.⁷

“Many patients who undergo surgical resection of their CSCC are later found, on full pathological evaluation, to be at high risk of recurrence. As the first and only immunotherapy approved in the adjuvant setting, Libtayo represents a practice-changing opportunity for this patient population, backed by compelling data showcasing its ability to significantly improve disease-free survival,” added Patel.

The randomized C-POST study enrolled 415 adult patients with local or regional CSCC at high risk for recurrence, after surgical resection and postoperative radiation therapy, randomized to receive either cemiplimab (n = 209) or placebo (n = 206) over 48 weeks.⁸ Patients received 350 mg of cemiplimab or placebo every 3 weeks for 12 weeks, followed by an increased dosage of 700 mg of cemiplimab or placebo every 6 weeks for up to 36 weeks.

Patients with high-risk CSCC are at risk for recurrence. While cemiplimab has been FDA-approved for treatment of advanced or metastatic CSCC since 2018 and is already the current standard of care,^3,6 the results of this trial are the first to demonstrate the performance of the agent in adjuvant treatment. The acceptance of the sBLA will expand cemiplimab’s clinical application in delaying recurrence, addressing this unmet need for this vulnerable group of patients.

REFERENCES:

1. FDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed October 8, 2025. https://tinyurl.com/5xst85m3

2. 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. Published January 13, 2025. Accessed September 23, 2025. https://tinyurl.com/y5pu8ybz

3. Rischin D, Porceddu S, Day F, et al. Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma. NEJM. Published online May 31, 2025. doi:https://doi.org/10.1056/nejmoa2502449

4. Libtayo® (cemiplimab) Phase 3 Data in the Adjuvant Treatment of Post-Surgical High-Risk Cutaneous Squamous Cell Carcinoma (CSCC) Have Potential to Be Practice-Changing. News release. Regeneron. Published May 31, 2025. Accessed September 23, 2025. https://tinyurl.com/5fp9t8vn

5. Regeneron Reports Second Quarter 2025 Financial and Operating Results. News release. Regeneron. Published August 1, 2025. Accessed September 23, 2025. https://tinyurl.com/ybjrjvr7

6. C-POST: Adjuvant Cemiplimab Reduces risk of Recurrence in Patients With High-Risk Cutaneous Squamous Cell Carcinoma. News release. ASCO Daily News. Published May 31, 2025. Accessed September 23, 2025. https://tinyurl.com/3xnp8v4a

7. 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. Accessed October 8, 2025. https://tinyurl.com/yc4v2kv8

8. Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma. ClinicalTrials.gov. Updated September 19, 2025. Accessed September 23, 2025. https://clinicaltrials.gov/study/NCT03969004