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In the Phase 3 LEAP-012 trial, KEYTRUDA plus LENVIMA in combination with TACE reduced the risk of disease progression or death by 34% compared to TACE alone
Late-breaking first interim analysis results are being presented during a Presidential Symposium session at the European Society for Medical Oncology Congress 2024
RAHWAY, N.J. & NUTLEY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai today announced results from the first interim analysis of the Phase 3 LEAP-012 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, plus LENVIMA® (lenvatinib), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, in combination with transarterial chemoembolization (TACE) compared to TACE alone for the treatment of patients with unresectable, non-metastatic hepatocellular carcinoma (HCC). These late-breaking data are being presented for the first time today during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2024 (Presentation #LBA3).
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After a median follow-up of 25.6 months (range, 12.6-43.5), KEYTRUDA plus LENVIMA in combination with TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.51-0.84]; p=0.0002) compared to TACE alone. Median PFS was 14.6 months (95% CI, 12.6-16.7) for the KEYTRUDA plus LENVIMA-based regimen versus 10.0 months (95% CI, 8.1-12.2) for TACE alone. At this analysis, a trend toward improvement in overall survival (OS), the trial’s other primary endpoint, was observed for the KEYTRUDA plus LENVIMA-based regimen versus TACE alone (HR=0.80 [95% CI, 0.57-1.11]; p=0.0867); 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.
“Hepatocellular carcinoma is one of the leading causes of cancer-related deaths worldwide, highlighting the need for new treatment options,” said Dr. Josep Llovet, Director of the Liver Cancer Program and Professor of Medicine at the Icahn School of Medicine at Mount Sinai. “These findings from the LEAP-012 trial demonstrate the potential of pembrolizumab plus lenvatinib in combination with TACE to extend progression-free survival for patients diagnosed with unresectable, non-metastatic disease.”
“Global incidence rates for hepatocellular carcinoma are expected to rise by more than 50 percent over the next two decades, and there have been limited advances for patients with unresectable, non-metastatic forms of disease,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “These results reflect our commitment to exploring therapeutic options for these patients, including in earlier stages of disease. We’re encouraged by the potential for another treatment option for patients with unresectable non-metastatic hepatocellular carcinoma in addition to the existing monotherapy indications for KEYTRUDA and LENVIMA.”
“Transarterial chemoembolization (TACE) has been a standard of care option for patients with unresectable, non-metastatic hepatocellular carcinoma for many years; however, many patients experience disease progression within one year,” said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai Inc. “Data from the Phase 3 LEAP-012 study demonstrate that the addition of KEYTRUDA plus LENVIMA to TACE may help address the unmet need for therapies that can improve progression-free survival for people with this disease. We are grateful to the patients and investigators for their participation in this study.”
Treatment was administered to 237 patients receiving the KEYTRUDA plus LENVIMA-based regimen and 241 patients receiving TACE alone. Treatment-related adverse events (TRAEs) 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% (n=4) versus 0.4% (n=1) 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.
KEYTRUDA plus LENVIMA is approved in the U.S., the EU, Japan and other countries for the treatment of advanced renal cell carcinoma (RCC) and certain types of advanced endometrial carcinoma. Lenvatinib is marketed as KISPLYX for advanced RCC in the EU. Merck and Eisai are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types, including but not limited to HCC, RCC, head and neck cancer, gastric cancer and esophageal cancer across multiple clinical trials.
Study design and additional data from LEAP-012
LEAP-012 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04246177) evaluating KEYTRUDA plus LENVIMA in combination with TACE versus dual placebo plus TACE for the treatment of patients with unresectable, non-metastatic HCC. The primary endpoints are PFS as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) following a maximum of five target lesions and with a requirement that new intrahepatic lesions must meet LI-RADS 5 criteria and OS. Secondary endpoints include objective response rate, duration of response, disease control rate, and time to progression as assessed by BICR per RECIST v1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), as well as PFS as assessed by BICR per mRECIST and safety. The study randomized 480 patients 1:1 to receive:
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