FDA Approves Adjuvant Cemiplimab for Cutaneous Squamous Cell Carcinoma

The FDA has approved cemiplimab-rwlc (Libtayo) for the adjuvant treatment of adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and radiation.1

The regulatory decision was supported by data from the phase 3 C-POST (NCT03969004), in which patients with CSCC at high risk of recurrence treated with cemiplimab achieved a median disease-feee survival (DFS) that was not reached (95% CI, not evaluable [NE]-NE) compared with 49.4 months (95% CI, 48.5-NE) for those treated with placebo (HR, 0.32; 95% CI, 0.20-0.51; P < .0001).

"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) at George Washington University School of Medicine & Health Sciences and director of the Cutaneous Oncology Program, GW Cancer Center, stated in a news release.2 “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, [cemiplimab] represents a practice-changing opportunity for this patient population, backed by compelling data showcasing its ability to significantly improve DFS.”

Notably, in September 2018, the FDA approved cemiplimab for the treatment of patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or curative radiation.3

How Did the C-POST Trial Evaluate Adjuvant Cemiplimab in High-Risk CSCC?

C-POST was a randomized, double-blind, multicenter, placebo-controlled phase 3 study that enrolled 415 patients with CSCC at high risk of recurrence after surgery and radiation.1 Patients needed to complete adjuvant radiation therapy within 2 to 10 weeks of randomization and have an ECOG performance status of 0 or 1. Investigators excluded patients with autoimmune disease requiring systemic immunosuppressant agents within 5 years of enrollment; a history of solid organ transplant; prior allogeneic or autologous stem cell transplantation; uncontrolled HIV, hepatitis B, or hepatitis C infection.

In part 1 of the study, patients were randomly assigned 1:1 to receive cemiplimab at 350 mg once every 3 weeks for 12 weeks, followed by cemiplimab at 700 mg once every 6 weeks for 36 weeks; or matching placebo given on the same schedule.4

Key stratification factors included tumor location (head and neck vs other), geographic region (North America vs Australia and New Zealand vs rest of world), high-risk category (nodal vs non-nodal), ECOG performance status (0 vs 1), and history of chronic lymphocytic leukemia (yes vs no).

In the open-label part 2 of the study, patients who experienced recurrence were given cemiplimab at 350 mg once every 3 weeks for up to 96 weeks. Notably, those in the experimental arm during part 1 were only allowed to participate in part 2 if they completed the full treatment course in part 1 and recurred at 3 months after the end of therapy.

DFS served as the trial's primary end point.

What Additional Efficacy Data Supported the Approval of Adjuvant Cemiplimab?

Additional findings from C-POST showed that among patients in the cemiplimab arm (n = 209), disease recurrence was reported in 9% of patients, including 4.8% who had distant recurrence and 3.8% who had locoregional recurrence. In the placebo arm (n = 206), 30% of patients experienced disease recurrence, including 13% and 17% with distant and locoregional recurrence, respectively.5

Deaths were reported in 2.9% of patients in the cemiplimab arm vs 1.9% of patients in the placebo arm.

What Adverse Effects Should I Be Aware of With Adjuvant Cemiplimab in High-Risk CSCC?

Findings from C-POST demonstrated that the safety profile of cemiplimab was consistent with previously reported data for the agent in patients with advanced cancers.2 The most common adverse effects (AEs) that occurred in at least 10% of patients in the cemiplimab and at a rate of at least 3% higher vs those given placebo included rash, pruritus, and hypothyroidism.

Serious AEs were reported in 18% of patients. The most common serious AEs that were observed in at least1% of patients in the experimental arm comprised pneumonia (1.5%), rash (1.5%), diarrhea (1.5%), adrenal insufficiency (1%), and arrhythmia (1%).

AEs led to permanent discontinuation of cemiplimab in 10% of patients, with the most common reported in at least 1% of patients consisting of increased alanine aminotransferase (ALT) levels, increased aspartate aminotransferase (AST) levels, increased blood alkaline phosphatase levels, and adrenal insufficiency.5

AEs led to dose interruptions in 22% of patients in the experimental arm, with the most common reported in at least 1% of patients comprising COVID-19, diarrhea, increased ALT levels, urinary tract infection, upper respiratory tract infection, increased AST levels, edema, dyspnea, pneumonitis, pneumonia, and rash.

What Is the Recommended Dose of Adjuvant Cemiplimab in High-Risk CSCC?

The prescribing information for cemiplimab includes warnings and precautions for immune-mediated adverse effects, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.1 For patients with high-risk CSCC, adjuvant cemiplimab is recommended at 350 mg once every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks, or 350 mg every 3 weeks until disease recurrence, unacceptable toxicity, or up to 48 weeks.

References

1. FDA approves cemiplimab-rwlc for adjuvant treatment of cutaneous squamous cell carcinoma. FDA. October 8, 2025. Accessed October 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-adjuvant-treatment-cutaneous-squamous-cell-carcinoma
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. October 8, 2025. Accessed October 8, 2025. https://investor.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-rwlc-approved-us-first-and-only
3. FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. September 28, 2018. Accessed October 8, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma
4. Rischin D, Porceddu S, Day F, et al. Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC). J Clin Oncol. 2025;43(suppl 16):6001. doi:10.1200/JCO.2025.43.16_suppl.6001
5. Libtayo. Prescribing information. Regeneron. Updated October 2025. Accessed October 8, 2025. https://www.regeneron.com/downloads/libtayo_fpi.pdf