Study of Cemiplimab Use in Hepatocellular Carcinoma Meets Primary End Points

Thomas Marron, PhD, MD, assistant director of early phase and immunotherapy clinical trials at the Tisch Cancer Institute and assistant professor of Medicine at the Icahn School of Medicine at Mount Sinai, discusses the end points of an exploratory study (NCT03916627) which examines the use of cemiplimab (Libtayo) in hepatocellular carcinoma (HCC).

The current landscape of HCC has seen a majority of tumors recur after hepatic resection. There have been no trials to demonstrate a survival advantage to using either pre-operative or post-operative, neoadjuvant or adjuvant therapy of any sort. 

Because of this, a multicenter study, which enrolled patients with tumors that could be excised, sought to find out if neoadjuvant cemiplimab could improve outcomes over hepatic resection in HCC, non-small cell lung cancer, and head and neck squamous cell carcinoma.

Participants received 2 cycles of cemiplimab given every 3 weeks. Four weeks after surgery ended, patients were given 8 cycles of adjuvant cemiplimab. Of the 20 patients that underwent surgery, 4 had a tumor necrosis of 70%, and 3 of the 4 who responded had a complete response. Tumor necrosis of 50% or more was also reported in 7 of the 20 patients, ultimately meeting the end points.

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0:08 | Our primary end point was significant tumor necrosis, which we defined as greater than 70% necrosis, unlike other cancer types, like lung cancer, where we have major pathologic response. This is then validated to correlate with overall survival, or in breast cancer, where we have pathologic complete response. Pathologic complete responses correlate well with overall survival in liver cancer because there's no standard neoadjuvant therapy, and there are no validated markers of response that correlate with survival.

0:38 | We came up with significant tumor necrosis looking at a small study from France, where they had resected patients following trans arterial chemoembolization. There, they show that around a 70% necrosis in the tumor that was resected correlated with a survival advantage. So, it's a totally different type of therapy. I am the first to admit that it is not a perfect endpoint, but we needed something to shoot for. So that was our primary end point. Our secondary end points dealt with delay of surgery, disease-free survival, overall response rate, and overall survival, and adverse events that were experienced.