Regeneron's cemiplimab (Libtayo) has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) as an adjuvant treatment for patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery. The findings come from the Phase 3 C-POST trial and suggest a potential new standard of care for this patient population.
The C-POST trial enrolled 415 patients with high-risk CSCC who had undergone surgery and postoperative radiation therapy. Participants were randomized to receive either 350 mg of intravenous cemiplimab or placebo every three weeks for the first 12 weeks, followed by 700 mg of cemiplimab or placebo intravenously every six weeks for 36 weeks. The primary endpoint was DFS, with secondary endpoints including freedom from locoregional recurrence, freedom from distant recurrence, overall survival (OS), cumulative incidence of second primary CSCC tumors, and safety.
Significant DFS Improvement
At the first prespecified interim analysis, with a median follow-up of 24 months (range, 2-64 months), cemiplimab reduced the risk of disease recurrence or death by 68% compared to placebo (HR = 0.32; 95% CI, 0.20-0.51; P < .0001). This indicates a substantial benefit in delaying or preventing recurrence in this high-risk group.
"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, MD, MBBS, FRACP, Research Lead, Head and Neck Cancer and Cutaneous SCC, Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, and 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 Profile
Adverse events (AEs) of any grade occurred in 91% of patients in the cemiplimab arm and 89% in the placebo arm. Grade 3 or higher AEs were more frequent in the cemiplimab arm (24%) compared to the placebo arm (14%). Treatment discontinuations due to AEs occurred in 10% and 1.5% of patients in the cemiplimab and placebo arms, respectively. Two patients in each arm experienced AEs leading to death.
Ongoing Evaluation
The C-POST trial is ongoing, with continued follow-up planned to evaluate overall survival. Regeneron plans to submit the data to the U.S. Food and Drug Administration (FDA) in the first half of 2025. Detailed results will be presented at an upcoming medical meeting.
Implications for CSCC Treatment
These results are particularly significant given the lack of approved adjuvant therapies for high-risk CSCC. Cemiplimab, a PD-1 inhibitor, has the potential to fill this unmet need and transform the treatment landscape for patients at high risk of recurrence following surgery and radiation therapy.
"Regeneron has long been a pioneer in non-melanoma skin cancer research. 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," said Israel Lowy, MD, PhD, Clinical Development Unit Head, Oncology, at Regeneron. "With these results, Libtayo now has the potential to also transform the treatment of high-risk resectable cutaneous squamous cell carcinoma 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."
