Regeneron Pharmaceuticals announced positive results from its Phase 3 C-POST trial, revealing that Libtayo (cemiplimab) significantly improved disease-free survival (DFS) as an adjuvant treatment in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery. The trial's success marks a potential advancement in treating this patient population, where recurrence rates can be high and treatment options are limited.
The C-POST trial enrolled 415 patients with high-risk CSCC, randomizing them to receive either Libtayo or a placebo for up to 48 weeks. The primary endpoint was DFS, measured from randomization to the first documented disease recurrence or death from any cause. At the first pre-specified interim analysis, with a median follow-up of 24 months, Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death compared to placebo (Hazard Ratio: 0.32; 95% CI: 0.20-0.51; p<0.0001).
Clinical Significance
"While surgery is curative for most people living with cutaneous squamous cell carcinoma, many are burdened with a higher risk of recurrence that can lead to death or disfiguration," said Danny Rischin, M.D., M.B.B.S., F.R.A.C.P., lead investigator of the trial. "At the first prespecified interim analysis, Libtayo achieved a remarkably high bar in improving disease-free survival in high-risk cutaneous squamous cell carcinoma. With no currently approved options in the adjuvant setting, these landmark results demonstrate Libtayo could represent a major advance in delaying recurrence in these vulnerable patients."
Safety and Tolerability
Safety was assessed in 205 patients in the Libtayo arm and 204 patients in the placebo arm. Adverse events of any grade occurred in 91% and 89% of patients in the Libtayo arm and the placebo arm, respectively. Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. Treatment discontinuations due to adverse reactions occurred in 10% and 1.5% of patients in the Libtayo arm and the placebo arm, respectively. Two patients experienced an AE leading to death in each arm.
Trial Design and Future Steps
The C-POST trial is ongoing and will continue for additional follow-up, including an analysis of the key secondary endpoint of overall survival. Regeneron plans to present detailed results at an upcoming medical meeting and submit them to the U.S. Food and Drug Administration (FDA) in the first half of 2025.
The trial included patients at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).
During the trial, Libtayo 350 mg or placebo was administered intravenously every three weeks for the first 12 weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks. Secondary endpoints include freedom from locoregional recurrence, freedom from distant recurrence, overall survival, cumulative incidence of second primary CSCC tumors, and safety.
Libtayo's Mechanism and Existing Approvals
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells. It has already been approved for certain patients with advanced CSCC, basal cell carcinoma, non-small cell lung cancer, and cervical cancer.
Regeneron's Commitment
"Regeneron has long been a pioneer in non-melanoma skin cancer research," said Israel Lowy, M.D., Ph.D., clinical development unit head, oncology, at Regeneron. "Libtayo was the first PD-1 inhibitor approved for certain patients with advanced cutaneous squamous cell carcinoma and has become a standard of care in this setting. With these results, Libtayo now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma with adjuvant treatment."
