Adjuvant Cemiplimab Boosts DFS in Cutaneous Squamous Cell Carcinoma

Investigators of the ongoing, double-blind, multicenter, global phase 3 C-POST trial (NCT03969004) are evaluating cemiplimab vs placebo as adjuvant therapy for those at a high risk of CSCC recurrence who had prior surgery and post-operative radiotherapy.

Adjuvant therapy with cemiplimab (Libtayo) produced a clinically meaningful and statistically significant disease-free survival (DFS) improvement vs placebo among patients who underwent surgery for high-risk cutaneous squamous cell carcinoma (CSCC), according to a press release on findings from the phase 3 C-POST trial (NCT03969004).¹

With a median follow-up of 24 months (range, 2-64) at the time of the first prespecified interim analysis, data showed that cemiplimab reduced the risk of disease recurrence or death by 68% compared with placebo (HR, 0.32; 95% CI, 0.20-0.51; P <.0001).

Among evaluable patients in the cemiplimab (n = 205) and placebo arms (n = 204), any grade adverse effects (AEs) affected 91% and 89%, respectively. The rate of grade 3 or higher AEs in each respective arm was 24% and 14%, and 10% and 1.5% discontinued study treatment following toxicity. Investigators noted that 2 patients in each arm had AEs resulting in death.

The trial’s investigators will continue to follow up with patients and analyze the key secondary end point of overall survival (OS). Additional findings will be shared at a future medical meeting and shared with regulatory health authorities. Developers plan to issue a regulatory submission to the FDA in the first half of 2025.

“While surgery is curative for most people living with [CSCC], many are burdened with a higher risk of recurrence that can lead to death or disfiguration. At the first prespecified interim analysis, [cemiplimab] achieved a remarkably high bar in improving [DFS] in high-risk [CSCC],” lead trial investigator Danny Rischin, MD, MBBS, FRACP, research lead in Head and Neck Cancer and Cutaneous SCC of the Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, stated in the press release.¹ “With no currently approved options in the adjuvant setting, these landmark results demonstrate [cemiplimab] could represent a major advance in delaying recurrence in these vulnerable patients.”

Investigators of the ongoing, double-blind, multicenter, global phase 3 C-POST trial are evaluating cemiplimab vs placebo as adjuvant therapy for those at a high risk of CSCC recurrence who had prior surgery and post-operative radiotherapy. A total of 415 patients were assigned to receive cemiplimab at 350 mg or placebo intravenously every 3 weeks for the first 12 weeks followed by cemiplimab at 700 mg or placebo intravenously every 6 weeks for 36 weeks.

The trial’s primary end point is DFS. Secondary end points include OS, freedom from distant recurrence, the cumulative occurrence of second primary CSCC, treatment-emergent AEs, and incidence of laboratory abnormalities.²

Patients 18 years and older with pathologically confirmed CSCC and macroscopic gross resection of all diseases were eligible for enrollment on the trial. Other requirements for study entry included having high-risk disease, completion of curative intent post-operative radiation within 2 to 10 weeks of randomization, and an ECOG performance status of 0 or 1. Patients were also required to have adequate hepatic, renal, and bone marrow function to enroll.

Those with squamous cell carcinomas arising in non-cutaneous sites or a concurrent malignancy other than localized CSCC were ineligible for enrollment on the trial.

“With these results, [cemiplimab] now has the potential to also transform the treatment of high-risk resectable [CSCC] with adjuvant treatment. This trial is a testament to our unrelenting commitment to investigating areas where patient need remains high and to pursuing clinical research across diverse stages of skin cancer,” Israel Lowry, MD, PhD, clinical development unit head of Oncology at Regeneron, the developers of cemiplimab, concluded.¹

References

1. 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 Pharmaceuticals, Inc. January 13, 2025. Accessed January 13, 2025. https://tinyurl.com/4fy8vcmh
2. 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, 2024. Accessed January 13, 2025. https://tinyurl.com/3vxdtfkp