Eisai and Merck & Co., Inc. Present Results from Phase 3 LEAP-002 Trial Evaluating LENVIMA (lenvatinib) Plus KEYTRUDA (pembrolizumab) Versus LENVIMA Monotherapy in Patients With Unresectable Hepatocellular Carcinoma
Findings to be featured in a late-breaking proffered paper session at European Society for Medical Oncology (ESMO) Congress 2022
TOKYO and RAHWAY, N.J., Sep 12, 2022 – (JCN Newswire) – Eisai and Merck & Co., Inc., Rahway, NJ, USA (referred to as MSD outside the USA and Canada) today announced the initial presentation of results from the ultimate analysis of the Phase 3 LEAP-002 trial investigating LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA versus LENVIMA monotherapy, as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). Email address details are being presented throughout a proffered paper session at the European Society for Medical Oncology (ESMO) Congress 2022, being held in Paris, France and virtually from Sept. 9-13 (abstract #LBA34).
In the ultimate analysis of the trial, there is a trend toward improvement for just one of the study’s dual primary endpoints, overall survival (OS), for patients treated with LENVIMA plus KEYTRUDA versus LENVIMA monotherapy; however, the outcomes didn’t meet statistical significance per the pre-specified statistical plan (HR=0.84 [95% CI: 0.71-1.00]; p=0.0227). The median OS was 21.2 months (95% CI: 19.0-23.6) for LENVIMA plus KEYTRUDA and 19.0 months (95% CI: 17.2-21.7) for LENVIMA monotherapy. Additionally, treatment with LENVIMA plus KEYTRUDA led to a trend toward improvement in the trial’s other dual primary endpoint of progression-free survival (PFS) versus LENVIMA monotherapy; however, the outcomes did not meet up with the pre-specified threshold at the initial interim analysis for statistical significance (HR=0.87 [95% CI: 0.73-1.02]; p=0.0466).
“The LEAP-002 trial reflects our research technique to build on evolving standards of care to improve outcomes for more folks with unresectable hepatocellular carcinoma,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck & Co., Inc., Rahway, NJ, USA Research Laboratories. “The median overall survival of 21.2 months seen with KEYTRUDA plus LENVIMA provides critical insights for further research in to the potential role of the combination.”
“As the outcome isn’t what we’d hoped, it is necessary for all of us to note that patients in the trial treated with LENVIMA monotherapy had a median overall survival of 19.0 months,” said Corina Dutcus, M.D., Senior Vice President, Clinical Research, Oncology at Eisai Inc. “Findings from the LEAP-002 trial can not only help advance our understanding and application of LENVIMA plus KEYTRUDA across our clinical development program but may also provide physicians with more information on LENVIMA monotherapy’s used in unresectable hepatocellular carcinoma, where it really is currently approved as cure option in multiple regions all over the world, like the U.S., europe (EU), Japan and China.”
LENVIMA monotherapy is approved for the first-line treatment of patients with uHCC in the U.S., the EU and China and for patients with uHCC in Japan. The approval of LENVIMA was predicated on outcomes 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.
LENVIMA (marketed as KISPLYX for renal cell carcinoma [RCC] in the EU) plus KEYTRUDA is approved in the U.S., the EU and Japan for the treating certain forms of advanced endometrial carcinoma and advanced RCC. Eisai and Merck & Co., Inc., Rahway, NJ, USA are studying the LENVIMA plus KEYTRUDA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in multiple tumor types, including however, not limited by endometrial carcinoma, HCC, melanoma, non-small cell lung cancer, RCC, head and neck cancer, colorectal cancer, gastric cancer and esophageal cancer, across a lot more than 15 clinical trials.
LEAP-002 study design and final analysis results (abstract #LBA34)
LEAP-002 is really a multicenter, randomized, double-blinded, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT03713593(New Window)) evaluating LENVIMA plus KEYTRUDA versus LENVIMA monotherapy for the first-line treatment of adult patients with uHCC. Patients were randomized 1:1 to get LENVIMA (12 mg orally once daily [for patients with screening bodyweight of at the very least 60 kg] or 8 mg orally once daily [for patients with screening bodyweight significantly less than 60 kg]) plus KEYTRUDA (200 mg intravenously [IV] on Day 1 of every three-week cycle); or LENVIMA (12 mg orally once daily [for patients with screening bodyweight of at the very least 60 kg] or 8 mg orally once daily [for patients with screening bodyweight significantly less than 60 kg]) plus saline placebo (IV administered on Day 1 of every three-week cycle). LENVIMA was administered until progressive disease or unacceptable toxicity. KEYTRUDA/placebo was administered for 35 cycles (approximately 2 yrs).
The dual primary endpoints were PFS, as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1; RECIST v1.1 has been modified because of this study to check out no more than 10 target lesions altogether and no more than five target lesions per organ), and OS. Objective response rate (ORR), as assessed by BICR per RECIST v1.1, was an integral secondary endpoint. The trial was made with two interim analyses and your final analysis for OS. Pre-specified efficacy boundaries were one-sided p=0.002 for PFS at interim analysis 1 and p=0.0185 for OS at the ultimate analysis.
By the info cut-off for the ultimate analysis (June 21, 2022), a complete of 794 patients were enrolled and treated, with a median follow-up of 32.1 months (range, 25.8-41.1). A complete of 534 OS events had occurred, with 36 patients (9.1%) in the combination arm and 24 patients (6.1%) in the LENVIMA monotherapy arm remaining on study treatment.
The median OS was 21.2 months (95% CI: 19.0-23.6) for LENVIMA plus KEYTRUDA versus 19.0 months (95% CI: 17.2-21.7) for LENVIMA monotherapy at the ultimate analysis. The median PFS was 8.2 months (95% CI, 6.4-8.4) for LENVIMA plus KEYTRUDA versus 8.0 months (95% CI: 6.3-8.2) for LENVIMA monotherapy at the initial interim analysis and 8.2 months (95% CI: 6.3-8.3) versus 8.1 months (95% CI: 6.3-8.3), respectively, at the ultimate analysis. The ORR was 26.1% (95% CI: 21.8-30.7) for LENVIMA plus KEYTRUDA versus 17.5% (95% CI: 13.9-21.6) for LENVIMA monotherapy at the ultimate analysis. Median duration of response was 16.six months (range, 2.0+ to 33.6+) in the KEYTRUDA plus LENVIMA arm versus 10.4 months (range, 1.9 to 35.1+) in the LENVIMA monotherapy arm at the ultimate analysis.
The safety profile of LENVIMA plus KEYTRUDA was in keeping with previously reported data on the combination. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 61.5% of patients treated with LENVIMA plus KEYTRUDA versus 56.7% of patients treated with LENVIMA monotherapy. Grade 5 TRAEs occurred in 1.0% of patients treated with LENVIMA plus KEYTRUDA versus 0.8% of patients treated with LENVIMA monotherapy. In patients treated with LENVIMA plus KEYTRUDA, the five most typical TRAEs of any grade were hypertension (43.3%), diarrhea (40.3%), hypothyroidism (40.0%), palmar-plantar erythrodysesthesia (PPE) syndrome (33.2%) and proteinuria (30.6%). In patients treated with LENVIMA monotherapy, the five most typical TRAEs of any grade were hypertension (46.8%), hypothyroidism (35.7%), proteinuria (34.9%), diarrhea (33.9%) and PPE syndrome (30.6%). Post-study systematic anti-cancer treatments received for 44.1% of patients receiving LENVIMA plus KEYTRUDA versus 52.1% of these receiving LENVIMA monotherapy.
Eisai Co., Ltd.
Merck & Co., Inc., Kenilworth, N.J., U.S.A.
Melissa Moody: +1-(215) 407-3536
Nikki Sullivan: +1-(718) 644-0730
Copyright 2022 JCN Newswire. All rights reserved. A division of Japan Corporate News Network.