Eisai Co., Ltd. announced that China's National Medical Products Administration (NMPA) has approved LENVIMA (lenvatinib mesylate) in combination with pembrolizumab and transarterial chemoembolization (TACE) for treating unresectable, non-metastatic hepatocellular carcinoma. This approval marks a significant advancement in treatment options for patients with this challenging form of liver cancer.
Clinical Trial Results Drive Approval
The approval is based on interim analysis results from the pivotal Phase III LEAP-012 trial, which demonstrated statistically significant and clinically meaningful improvements in patient outcomes. The combination therapy reduced the risk of disease progression or death by 34% compared to TACE alone (Hazard Ratio [HR]=0.66 [95% Confidence Interval (CI), 0.51-0.84]; p=0.0002).
Median progression-free survival (PFS), one of the trial's primary endpoints, was 14.6 months (95% CI, 12.6-16.7) for the combination therapy compared to 10.0 months (95% CI, 8.1-12.2) for TACE alone. The trial also showed a trend toward improvement in overall survival (OS), the other primary endpoint, with an HR of 0.80 (95% CI, 0.57-1.11; p=0.087) for the combination therapy versus TACE alone.
Safety Profile and Patient Population
The LEAP-012 trial enrolled 478 patients, with 237 receiving the combination therapy and 241 receiving TACE alone. Treatment Emergent Adverse Events (TEAEs) occurred in 99.6% of patients receiving the combination therapy versus 96.7% of patients receiving TACE alone. Grade 3, 4, or 5 TEAEs occurred in 82.3% of patients receiving the combination therapy versus 47.7% for TACE alone.
The combination therapy led to discontinuation of both study drugs in 13.1% of patients compared to 4.1% for TACE alone. TEAEs led to death in 4.2% of patients receiving the combination therapy versus 2.5% of patients receiving TACE alone.
Addressing Critical Medical Need in China
Liver cancer represents one of the leading causes of cancer-related deaths worldwide. In 2022, China accounted for approximately 367,000 new liver cancer cases and 316,000 deaths, representing more than 40% of global cases and deaths. Hepatocellular carcinoma is the most common type of liver cancer, representing approximately 90% of primary liver cancer cases.
TACE has been a standard of care for patients with unresectable, non-metastatic HCC for many years. However, many patients experience disease progression within one year, creating an urgent need for new treatment options.
Expanding Treatment Access
LENVIMA monotherapy has been approved for treating patients with unresectable HCC in more than 80 countries, including Japan, the United States, Europe, and China. The drug was first launched in China in November 2018 as the first new systemic therapy in approximately ten years available for first-line treatment of unresectable HCC.
This new combination approval is expected to further expand LENVIMA's contribution to patients with hepatocellular carcinoma in China. The approval builds on Eisai's strategic collaboration with Merck & Co., Inc., Rahway, established in March 2018 for the worldwide co-development and co-commercialization of lenvatinib.
Mechanism of Action
LENVIMA is an orally administered kinase inhibitor discovered and developed in-house by Eisai. The drug features a novel binding mode that selectively inhibits multiple activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4), in addition to other pathway-related RTKs involved in tumor angiogenesis, tumor progression and modification of tumor immunity.
