Background of the LEAP-002 Trial Evaluating Lenvatinib Monotherapy in uHCC

Richard S. Finn, MD, professor of medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, discusses the background on lenvatinib (Lenvima) and what led to the development of the LEAP-002 trial (NCT03713593).

The multikinase inhibitor, lenvatinib, was previously approved by the FDA based on data from the REFLECT study (NCT01761266). In this trial, lenvatinib was seen to be non-inferior to sorafenib (Nexavar) in terms of overall survival.

This led investigators to evaluate the use of lenvatinib in the first-line for patients with unresectable hepatocellular carcinoma in the phase 3 LEAP-002 study. The final analysis of this study was presented at ESMO Congress 2022.

Transcription:

0:08 | Lenvatinib is a multikinase inhibitor that has been approved in the United States for some years now, globally, based on the results of the REFLECT study, which demonstrated it to be non-inferior to sorafenib in terms of overall survival. In that study of advanced liver cancer patients, lenvatinib had a survival of just over 13 months, but was superior to sorafenib in terms of secondary end points, progression-free survival and objective response rate.

0:37 | At the same time, pembrolizumab is a PD-1 antibody which is approved in the United States from an accelerated approval mechanism based on objective response rate, duration of response, and safety. That is in a second line setting, and its activity has been confirmed and phase 3 studies, KEYNOTE-240 [NCT02702401], and KEYNOTE-394 [NCT03062358], 2 studies of pembrolizumab in the second-line setting vs placebo. KEYNOTE-240 just missed its primary end point, whereas KEYNOTE-394 confirmed its activity.

1:20 | Given that there's evolving data that there could be a synergistic interaction between a kinase inhibitor like lenvatinib and its effect on multiple kinases in the immune microenvironment, it was evaluated in combination with lenvatinib initially in a phase 1B study. This phase 1B study was in advanced liver cancer in the frontline setting. We published this in the Journal of Clinical Oncology in 2020 and showed that the combination had an objective response rate of about 36% and an overall survival of over 21 months. That was the basis for LEAP-002.