Merck & Co (MSD) and Eisai are set to discontinue their Phase III clinical trial for unresectable, non‑metastatic hepatocellular carcinoma (HCC) as Keytruda (pembrolizumab) plus Lenvima (lenvatinib), along with transarterial chemoembolisation (TACE), failed to achieve statistical significance for overall survival (OS).
OS is one of the primary goals of the LEAP-012 Phase III trial.
Eisai discovered the orally available multiple receptor tyrosine kinase inhibitor (TKI) Lenvima while Keytruda is MSD’s anti-programmed death-1 (PD-1) therapy.
A pre‑specified interim analysis revealed that the combination with TACE was compared to TACE alone.
The safety profile of this regimen was observed to be consistent with prior studies of the combination and earlier LEAP‑012 analyses.
The companies reported that the likelihood of achieving the protocol‑specified threshold for OS statistical significance at a future analysis was low. Investigators are being informed, and further analysis of the outcomes is underway.
MSD and Eisai plan to work with study investigators to share the data with the scientific community.
Previously, LEAP012 met its other primary endpoint of progression free survival (PFS), showing a statistically significant improvement over TACE alone.
Results from the first interim analysis served as the final analysis for PFS endpoint. With further follow-up during later analyses, PFS continued to be consistent.
MSD Research Laboratories global clinical development vice-president Dr Gregory Lubiniecki said: “Although the PFS results from this study are encouraging, unfortunately, the addition of Keytruda plus Lenvima to TACE did not show the overall survival benefit we hoped.
“We are grateful to the patients and investigators for their important contributions to this study, and our commitment is unwavering as we pursue new therapeutic options for people living with hepatocellular carcinoma, an aggressive and challenging-to-treat cancer.”
In May 2024, MSD announced its Phase III KEYNOTE-B21 (ENGOT-en11/GOG-3053) trial of Keytruda plus chemotherapy in patients with newly diagnosed high-risk endometrial cancer following surgery with curative intent, had failed to meet its primary endpoint.
