Merck and Eisai announced that the Phase 3 LEAP-002 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, versus LENVIMA monotherapy did not meet its dual primary endpoints of overall survival (OS) and progression-free survival (PFS) as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

There were trends toward improvement in OS and PFS for patients who received KEYTRUDA plus LENVIMA versus LENVIMA monotherapy; however, these results did not meet statistical significance per the pre-specified statistical plan. The median OS of the LENVIMA monotherapy arm in LEAP-002 was longer than that observed in previously reported clinical trials evaluating LENVIMA monotherapy in uHCC.

The safety profile of KEYTRUDA plus LENVIMA was consistent with previously reported data on the combination. 

“Our joint clinical development program for KEYTRUDA plus LENVIMA is designed to address unmet needs for some of the most challenging-to-treat types of cancer, like hepatocellular carcinoma,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Developement, Merck Research Laboratories. “We remain confident in the potential of this combination based on the body of evidence we’ve seen to date and will continue to investigate its role across multiple types of cancer.”

“Aiming for further improvement in the treatment of patients with unresectable HCC, we selected LENVIMA monotherapy, a standard of care option, as the control arm of the LEAP-002 trial,” said Corina Dutcus, M.D., Senior Vice President, Clinical Research, Oncology at Eisai Inc. “While results evaluating the combination are not what we had hoped for, we will continue to contribute to the care of patients with unresectable HCC by applying valuable knowledge from the LEAP-002 trial.”

LENVIMA monotherapy is approved for the first-line treatment of patients with uHCC in the U.S., Europe, and China, and for patients with uHCC in Japan. The approval of LENVIMA was based on results of the Phase 3 REFLECT trial which evaluated the efficacy and safety of LENVIMA versus sorafenib for the first-line treatment of patients with uHCC.

Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in more than 10 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, biliary tract cancer, colorectal cancer, gastric cancer, esophageal cancer, glioblastoma and pancreatic cancer) across more than 15 clinical trials.