Dr. Finn on the Rationale for the Phase III KEYNOTE-240 Trial in HCC

Richard S. Finn, MD, professor of clinical medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine, University of California, Los Angeles (UCLA), and Director of the Signal Transduction and Therapeutics Program at the Jonsson Comprehensive Cancer Center at UCLA, discusses the rationale for the phase III KEYNOTE-240 trial in hepatocellular carcinoma (HCC).

Checkpoint inhibitors have made a dramatic impact on the treatment landscape of oncology, says Finn. Initial research in HCC led to several single-arm phase II trials with nivolumab (Opdivo) and pembrolizumab (Keytruda). These trials showed promising response rates ranging from 15% to 20% in pretreated populations. Moreover, these responses were found to be durable, reaching a year in some cases. Although kinase inhibitors and antiangiogenic agents like ramucirumab (Cyramza) have been shown to improve survival, they do show significant response rates as well, adds Finn.

An additional advantage of checkpoint inhibitors is that they are also well tolerated, although AST/ALT levels should be carefully monitored due to underlying cirrhosis. Based on the phase II data from the CheckMate-040 and KEYNOTE-224 trials, both nivolumab and pembrolizumab were granted accelerated approvals by the FDA. Given that accelerated approvals are contingent on randomized data, the phase III KEYNOTE-240 trial was launched to confirm the activity of second-line pembrolizumab in advanced HCC. Although the trial failed to meet its primary endpoints, pembrolizumab conferred a clinically meaningful benefit for patients with prior exposure to sorafenib (Nexavar).