Eisai and Merck Announce Results of Phase 3 LEAP-002 Trial Evaluating LENVIMA (lenvatinib) plus KEYTRUDA (pembrolizumab) versus LENVIMA alone Medication for unresectable hepatocellular carcinoma
Findings to be presented at the latest paper session at the European Society of Medical Oncology (ESMO) Congress 2022
Tokyo and New Jersey Lowe, NJ, Sept. 12, 2022–(JCN Newswire)–Eisai and Merck & Co., Lowe, NJ, USA (known as MSD outside the U.S. and Canada) today announced the first demonstration of LEAP-002 Phase 3 Final analysis of the trial investigating Eisai’s discovery of the oral multi-receptor tyrosine kinase inhibitor LENVIMA and Merck & Co., Inc., Rahway’s anti-PD-1 therapy KEYTRUDA, New Jersey State, United States with LENVIMA monotherapy as first-line therapy for patients with unresectable hepatocellular carcinoma (uHCC). Results will be presented in a paper conference at the 2022 European Society of Medical Oncology (ESMO) Congress, September 9-13 in Paris, France (Abstract #LBA34).
At the final analysis of the trial, there was a trend toward improvement in overall survival (OS), one of the study’s dual primary endpoints, for patients receiving LENVIMA plus KEYTRUDA versus LENVIMA monotherapy; however, according to The prespecified statistical plan did not meet statistical significance (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) with LENVIMA plus KEYTRUDA and 19.0 months (95% CI: 17.2-21.7) with LENVIMA monotherapy. In addition, treatment with LENVIMA plus KEYTRUDA resulted in a trend toward improvement in progression-free survival (PFS), the trial’s other dual primary endpoint, compared with LENVIMA monotherapy; however, in the first interim analysis, results did not meet a prespecified threshold , for statistical significance (HR=0.87 [95% CI: 0.73-1.02]; p=0.0466).
“The LEAP-002 trial reflects our research strategy of building on an evolving standard of care to further improve more unresectable hepatocellular carcinomas patient outcomes,” said Gregory Lubiniecki, PhD, vice president of global clinical development at Merck & Co., Inc., Rahway, NJ, U.S. Research Laboratories. “The median overall survival with KEYTRUDA plus LENVIMA was 21.2 months, providing important insights for further investigation of the potential role of this combination.”
“Although the results are not What we had hoped, importantly, we saw that patients in the trial who received LENVIMA monotherapy had a median overall survival of 19.0 months,” said Corina Dutcus, MD, senior vice president of clinical research, Eisai Oncology. “The findings from the LEAP-002 trial will not only help advance our understanding and use of LENVIMA plus KEYTRUDA in our clinical development program, but will also provide physicians with more insight into LENVIMA monotherapy in unresectable hepatocellular carcinoma. More information, it is currently approved as a treatment option in multiple regions around the world, including the United States, European Union (EU), Japan and China. With uHCC in t uHCC patients in the United States, European Union and China and Japan. The approval of LENVIMA is Based on the results of the phase 3 REFLECT trial, which evaluated the efficacy and safety of LENVIMA versus sorafenib in first-line treatment of patients with uHCC.
LENVIMA (treated with KISPLYX in the EU) Renal Cell Carcinoma [RCC] marketing) plus KEYTRUDA is approved in the U.S., EU and Japan for the treatment of certain types of advanced endometrial cancer and advanced RCC. Eisai and Merck & Co. of Rawai, NJ, U.S.A. LEnvatinib and Pembrolizumab) clinical plans to study LENVIMA in combination with KEYTRUDA in multiple tumor types, including but not limited to endometrial cancer, HCC, melanoma, non-small cell lung cancer, renal cell cancer, head and neck cancer, colorectal cancer, gastric cancer and Esophageal Cancer, Over 15 Clinical Trials.
LEAP-002 Study Design and Final Analysis Results (Abstract #LBA34)
LEAP-002 is a multicenter, randomized, double-blind, active-controlled Phase 3 trial (ClinicalTrials.gov, NCT03713593 (New Window )) to evaluate LENVIMA plus KEYTRUDA versus LENVIMA monotherapy as first-line therapy in adult patients with uHCC. Patients were randomized in a 1:1 ratio to receive LENVIMA (12 mg orally once daily [for patients with a screening weight of at least 60 kg] or once daily orally) 8 mg [for patients with screening weight less than 60 kg]) plus KEYTRUDA (intravenous [IV] 200 mg on Day 1 of every three-week cycle); or LENVIMA (12 mg orally once daily [for screening weight at least 60 kg]) kg of patients] or 8 mg orally once daily [for patients with screening weight less than 60 kg]) plus saline placebo (intravenous on Day 1) every three-week cycle). Administer LENVIMA until disease progression or unacceptable Toxicity of KEYTRUDA/placebo for up to 35 cycles (approximately two years).
The dual primary endpoint was PFS, determined by each reverse Blinded Independent Central Review (BICR) Evaluation Criteria for Solid Tumors, version 1.1 (RECIST v1.1; RECIST v1.1 has been modified for this study to track up to 10 target lesions and up to 5 targets per organ lesions) and OS. Objective response rate (ORR) as assessed by BICR according to RECIST v1.1 was a key secondary endpoint. The trial was designed with two interim analyses and one final OS analysis. In the interim analysis 1, the prespecified efficacy margin for PFS was one-sided p=0.002 and for OS in the final analysis p=0.0185.
As of data cutoff – as of final analysis (June 21, 2022), a total of 794 patients were enrolled and treated with a median follow-up of 32.1 months ( range, 25.8-41.1). A total of 534 OS events occurred, of which 36 patients (9.1%) in the combination arm and 24 patients (6.1%) in the LENVIMA monotherapy arm remained on study treatment.
At the final analysis, the median OS for LENVIMA plus KEYTRUDA was 21.2 months (95% CI: 19.0-23.6), while the median OS for LENVIMA monotherapy was 21.2 months (95% CI: 19.0-23.6) was 19.0 months (95% CI: 17.2-21.7). Median PFS was 8.2 months (95% CI, 6.4-8.4) with LENVIMA plus KEYTRUDA versus 8.0 months (95% CI: 6.3-8.2) and 8.2 months with LENVIMA monotherapy at the first interim analysis (95% CI: 6.3-8.3) ) and 8.1 months (95% CI: 6.3-8.3) respectively in the final analysis. In the final analysis, the ORR was 26.1% (95% CI: 21.8-30.7) with LENVIMA plus KEYTRUDA, compared with 17.5% (95% CI: 13.9-21.6) with LENVIMA monotherapy. At the final analysis, the median duration of response was 16.6 months (range, 2.0+ to 33.6+) in the KEYTRUDA plus LENVIMA group compared with 10.4 months (range, 1.9 to 35.1+) in the LENVIMA monotherapy group.
The safety profile of LENVIMA plus KEYTRUDA was consistent with previously reported combination data. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 61.5% of patients receiving LENVIMA plus KEYTRUDA compared to 56.7% of patients receiving LENVIMA monotherapy. Grade 5 TRAEs occurred in 1.0% of patients receiving LENVIMA plus KEYTRUDA compared to 0.8% of patients receiving LENVIMA monotherapy. Among patients treated with LENVIMA plus KEYTRUDA, the five most common TRAEs of any grade were hypertension (43.3%), diarrhea (40.3%), hypothyroidism (40.0%), palmoplantar erythema (PPE) syndrome ( 33.2%) and proteinuria. 30.6%). Among patients receiving LENVIMA monotherapy, the five most common TRAEs of any grade were hypertension (46.8%), hypothyroidism (35.7%), proteinuria (34.9%), diarrhea (33.9%) and PPE combined symptoms (30.6%). The proportion of patients receiving LENVIMA plus KEYTRUDA received post-study systemic anticancer therapy was 44.1%, compared with 52.1% of patients receiving LENVIMA monotherapy.
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