Cemiplimab Boosts Disease-Free Survival Post-Surgery in High-Risk CSCC

Regeneron Pharmaceuticals has reported promising findings from their Phase 3 C-POST trial, which examined the effects of the PD-1 inhibitor Libtayo (cemiplimab) in patients with high-risk cutaneous squamous cell carcinoma (CSCC) following surgery. These results mark a significant breakthrough, as Libtayo is the first immunotherapy to demonstrate a noteworthy improvement in disease-free survival (DFS) in such high-risk patients, compared to placebo. This comes in the wake of a recent Phase 3 trial with Keytruda, another immunotherapy, which did not succeed in the same context.

The C-POST trial enrolled 415 individuals who had undergone surgery and displayed a high risk of CSCC recurrence. These participants were randomly assigned to receive either Libtayo or a placebo for a maximum duration of 48 weeks. The primary goal was to assess DFS, which refers to the time elapsed from the start of the study until the first instance of disease recurrence or death from any cause. At a median follow-up period of 24 months, Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death when compared to the placebo group, a statistically significant result with a hazard ratio of 0.32 and p-value less than 0.0001.

Safety evaluations revealed that 91% of patients in the Libtayo group experienced adverse events (AEs) of varying severity, compared to 89% in the placebo group. Severe AEs (Grade ≥3) were observed in 24% of those receiving Libtayo, as opposed to 14% among placebo recipients. Treatment discontinuations due to adverse reactions occurred in 10% of Libtayo patients, a noteworthy contrast to the 1.5% in the placebo cohort. Additionally, each arm of the trial experienced two cases of AEs leading to death.

With these interim results, the C-POST trial will continue for further follow-up, including a review of the secondary endpoint focusing on overall survival. More comprehensive data will be presented at an upcoming medical conference and shared with regulatory bodies, with plans for a submission to the U.S. FDA in the first half of 2025.

Dr. Danny Rischin, the trial's lead investigator and Head of the Head and Neck Cancer and Cutaneous SCC Department of Medical Oncology at the Peter MacCallum Cancer Centre in Melbourne, emphasized the significance of these findings. He noted that, although surgery can be curative for many living with CSCC, high-risk patients face a considerable chance of recurrence, which can lead to severe consequences, including death or disfigurement. Therefore, these groundbreaking results suggest that Libtayo could offer a substantial advancement in delaying recurrence in these vulnerable patients.

Dr. Israel Lowy, Clinical Development Unit Head, Oncology, at Regeneron, also commented on the impact of these results. He highlighted Regeneron's commitment to advancing cancer treatments, particularly for conditions with high unmet needs, and the transformative potential Libtayo has demonstrated in the adjuvant treatment of high-risk resectable CSCC.

The C-POST trial is a placebo-controlled, double-blind, global study evaluating Libtayo's efficacy as an adjuvant treatment post-surgery and radiation therapy in patients with high-risk CSCC characteristics. This includes nodal features like extracapsular extension or multiple involved lymph nodes, as well as non-nodal features such as in-transit metastases and locally recurrent tumors with poor prognostic markers. The trial's primary endpoint is DFS, with secondary endpoints covering freedom from both locoregional and distant recurrence, overall survival, and the incidence of second primary CSCC tumors, in addition to safety.

Libtayo, developed using Regeneron's VelocImmune technology, is a fully human monoclonal antibody targeting the PD-1 receptor on T cells. It works by preventing cancer cells from suppressing T-cell activation through the PD-1 pathway. Already approved in over 30 countries for various cancers, including advanced CSCC, Libtayo continues to be investigated for its potential in diverse oncological settings.