Neoadjuvant cemiplimab/SBRT improves DFS in resectable HCC

According to the results of the 2 phase trial (NCT03916627) published in 2025, when neoadjuvant cimipilimab (Cemiplimab) -Libtayo in patients with hepatocellular carcinoma, 2 year disease-free survival (DFS) was favorable and rates of significant tumor necrosis (STN) were similar between treatment groups.

The DFS rate 79% at 1 year in the cimipilimab-only group (95%CI, 53%-92%< /span>), while the cimepilimab combined with SBRT group was 88% (95%CI, 59%-97%). At 2 years, the incidence of DFS was 62% (95% confidence interval [CI] , 36%-80%) and 88% (95%CI, 59%-97%). A total of 20% of patients in the cimepilimab monotherapy group experienced STN, compared with 19% in the cimepilimab plus SBRT group. The complete tumor necrosis rates were 15% and 13% respectively.

The Kaplan-Meier curve is used to analyze factors affecting DFS. Based on STN pathological response exceeding 70% versus 70% or less without STN pathological response, the HR was 0.42 (P=0.39). For patients with a preoperative reduction in circulating tumor DNA (ctDNA) of more than 50% versus 50% or less, the HR was 0.55 (P=0.32). For postoperative MRD negative or positive minimal residual disease (MRD), the HR was 0.18 (P=0.002).

ctDNA kinetics studied molecular fold changes in mutated tumors over time in response to pathological responses using cimipilimab alone and cimipilimab plus SBRT. The results showed that ctDNA was correlated with tumor size (r=0.84; P<0.001).

Neoadjuvant therapy-related adverse reactions (TRAEs) occurred in 29% of patients compared with 55% in the combination group, and adjuvant TRAEs occurred in 39% vs. 67%. Grade 3 or higher TRAE occurred in 9.5% vs. 0% in the neoadjuvant treatment group and 17% vs. 0% in the adjuvant treatment group. The incidence of serious adverse reactions was 5% vs. 0% in the neoadjuvant setting and 17% vs. 0% in the adjuvant setting.

Patients who received two years of DFS and neoadjuvant therapy were more favorable compared with historical controls. Patients who received cimipilimab plus SBRT had better relapse-free survival compared with patients who received cimepilimab alone. Neoadjuvant immunotherapy with cimepilimab has an acceptable safety profile with or without SBRT. ”

Patients were included in the cimepilimab monotherapy group (n=21), with 350mg every 3 weeks for 2 cycles, or the cimepilimab combined with SBRT treatment group (t=21), use 8Gy of SBRT in 3 times within 1 weeks, and use 350mg of cimepilimab every 3 weeks for 3 cycles. In both groups, patients then continued with surgery and then received another round of cimipilimab at 350 mg every 3 weeks for a total of 8 cycles. In the combination treatment group, patients were followed for 5 years.

The primary endpoint was STN, and secondary endpoints were DFS and the incidence of adverse events. Exploratory endpoints include ctDNA assessment and pharmacodynamic assessment. ctDNA was collected before the first and second doses of the new adjuvant cimeplimab; 4 weeks postoperatively; during the first dose of adjuvant cimepilimab; during the adjuvant cimeplimab treatment on day 1 of cycle 2; and followed for 30 days.

The cutoff date of July 31, 2025 shows that the last patient had been on the study for approximately 24 months after undergoing surgical resection on August 23, 2023. The median follow-up time was 41 months after resection. Between arms, 61% of patients were 65 years or older, 83% were male, 51% were Asian, and 76% were not Hispanic or Latino. Additionally, 88% of patients had an ECOG performance status of 0, 58% had tumors larger than 5cm, and 86% had 1 tumors.

References: https://www.cancernetwork.com/view/neoadjuvant-cemiplimab-sbrt-yields-improved-dfs-in-resectable-hcc