Merck, Eisai announce results from interim analysis of Phase 3 LEAP-012 trial

Merck (MRK) and Eisai (ESAIY) announced results from the first interim analysis of the Phase 3 LEAP-012 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with transarterial chemoembolization compared to TACE alone for the treatment of patients with unresectable, non-metastatic hepatocellular carcinoma. These late-breaking data were presented for the first time during a Presidential Symposium at the European Society for Medical Oncology Congress 2024. After a median follow-up of 25.6 months, KEYTRUDA plus LENVIMA in combination with TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, reducing the risk of disease progression or death by 34% compared to TACE alone. Median PFS was 14.6 months for the KEYTRUDA plus LENVIMA-based regimen versus 10.0 months for TACE alone. At this analysis, a trend toward improvement in overall survival, the trial’s other primary endpoint, was observed for the KEYTRUDA plus LENVIMA-based regimen versus TACE alone; the OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial is continuing, and follow-up of OS is ongoing. The safety profile of the KEYTRUDA plus LENVIMA-based regimen was consistent with that observed in previously reported studies evaluating the combination. Treatment was administered to 237 patients receiving the KEYTRUDA plus LENVIMA-based regimen and 241 patients receiving TACE alone. Treatment-related adverse events occurred in 98.7% of patients receiving KEYTRUDA plus LENVIMA in combination with TACE versus 84.6% of patients receiving TACE alone and led to the discontinuation of both study drugs in 8.4% versus 1.2% of patients, respectively. Serious adverse events were observed in 33.3% of patients receiving KEYTRUDA plus LENVIMA in combination with TACE versus 12.4% of patients receiving TACE alone. Grade 3 or 4 TRAEs occurred in 71.3% of patients receiving KEYTRUDA plus LENVIMA in combination with TACE versus 31.1% for TACE alone, and TRAEs led to death in 1.7% versus 0.4% of patients, respectively. LENVIMA monotherapy is approved for the treatment of patients with unresectable HCC in more than 80 countries, including in the U.S., Europe, China and Japan. KEYTRUDA is approved as a monotherapy for the treatment of patients with HCC secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen in the U.S. and as a monotherapy for the treatment of patients with HCC who have been previously treated with sorafenib or oxaliplatin-containing chemotherapy in China.