LENVIMA(R) (lenvatinib) Plus KEYTRUDA(R) (pembrolizumab) in Combination With Transarterial Chemoembolization (TACE) Significantly Improved Progression-Free Survival Compared to TACE Alone in Patients With Unresectable, Non-Metastatic Hepatocellular Carcinoma (HCC)
TOKYO and RAHWAY, N.J., Sept 17, 2024 - (JCN Newswire via SeaPRwire.com) - Eisai and Merck & Co., Inc., Rahway, NJ, USA (known as MSDoutside of the United States and Canada) today announced results from the first interim analysis of the Phase 3 LEAP-012 trial evaluating LENVIMA® (lenvatinib), the orally available multiple receptor tyrosine kinase inhibitor (TKI)discovered by Eisai, plus KEYTRUDA® (pembrolizumab), the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, 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 were presented for the first time on September 14 (Central European Summer Time) during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2024 (Presentation #LBA3).After a median follow-up of 25.6 months (range, 12.6-43.5), LENVIMA plus KEYTRUDA 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 toTACE alone. Median PFS was 14.6 months (95% CI, 12.6-16.7) for the LENVIMA plus KEYTRUDA-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 primaryendpoint, was observed for the LENVIMA plus KEYTRUDA- 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, andfollow-up of OS is ongoing. The safety profile of the LENVIMA plus KEYTRUDA- 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,1,2” 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 lenvatinib plus pembrolizumab 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, 3” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, MSD Research Laboratories. “These resultsreflect 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,4,5,6,7” said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead atEisai Inc. “Data from the Phase 3 LEAP-012 study demonstrate that the addition of LENVIMA plus KEYTRUDA toTACE may help address the unmet need for therapies that can improve progression-free survival for people with thisdisease. 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 LENVIMA plus KEYTRUDA in combination with TACE versus 84.6% of patients receiving TACEalone 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 LENVIMA plus KEYTRUDA in combination with TACE versus12.4% of patients receiving TACE alone. Grade 3 or 4 TRAEs occurred in 71.3% of patients receiving LENVIMA plusKEYTRUDA 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 Japan, the U.S., Europe and China.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 amonotherapy for the treatment of patients with HCC who have been previously treated with sorafenib or oxaliplatin-containing chemotherapy in China.LENVIMA plus KEYTRUDA 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 marketedas KISPLYX® for advanced RCC in the EU. Eisai and Merck & Co., Inc., Rahway, NJ, USA are studying the LENVIMA plus KEYTRUDA 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.About LEAP-012LEAP-012 is a multicenter, randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04246177) evaluating LENVIMA plus KEYTRUDA 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 amaximum 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 toprogression 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:LENVIMA (12 mg [for participants with screening body weight ≥60 kg] or 8 mg [for participants with screeningbody weight
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