Sep 12, 2017 22:54 JST
Source: Eisai
|
|
Eisai Presents Results of Phase Ib/II Clinical Study of Lenvima (Lenvatinib) in Combination with Pembrolizumab for Renal Cell Carcinoma in Oral Session at ESMO 2017 Congress
TOKYO, Sep 12, 2017 - (JCN Newswire) - Eisai Co., Ltd. announced today that an oral presentation on the results of the renal cell carcinoma cohort from a Phase Ib/II clinical study of its in-house discovered and developed multiple receptor tyrosine kinase inhibitor lenvatinib mesylate (product names: Lenvima / Kisplyx, "lenvatinib") in combination with the Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside of the United States and Canada) anti-PD-1 therapy pembrolizumab (product name: KEYTRUDA) developed by was given at the European Society for Medical Oncology (ESMO) 2017 Congress(1), which took place in Madrid, Spain. This combination therapy is being jointly developed by both companies.
The presentation at the ESMO 2017 Congress highlighted an analysis of 30 patients with metastatic renal cell carcinoma enrolled in combined Phase Ib and Phase II parts as of March 1, 2017. Based on the results of the analysis (investigator review), the primary endpoint of the Phase II part, Objective Response Rate* at 24 weeks after treatment began (ORR Week24) was 63%, with tumor regression observed in 93% (n = 28) of patients since beginning treatment (baseline). A tumor response was observed regardless of whether patients had previously received treatment or not (see table below).
http://www.acnnewswire.com/topimg/Low_Eisai91117Table.jpg
Additionally, tumor response was observed regardless of whether PD-L1 was expressed or not. In this study, the most frequently observed adverse events (top 6) were diarrhea, fatigue, hypothyroidism, stomatitis, hypertension and nausea.
In 2012, the number of patients with renal cancer was estimated to be approximately 338,000 worldwide,including approximately 115,000 in Europe, 58,000 in the United States and 17,000 in Japan.(2) Renal cellcarcinoma comprises more than 90% of all malignancies of the kidney,(3) and originates from malignant cells in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people over 55 years of age is rising, and it is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy.
However with low 5-year survival rates, this remains a disease with significant unmet medical need. Eisai regards oncology as a key therapeutic area and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai remains committed to providing further clinical evidence for this combination therapy aimed at earlier submission for renal cell carcinoma as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.
*Objective Response Rate: The ratio of patients whose tumor size decreased by at least 30% (Partial Response) or disappeared (Complete Response) after treatment.
About lenvatinib mesylate (product names: Lenvima, Kisplyx, "lenvatinib")
Discovered and developed in-house, lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and RET) involved in tumor proliferation.
Currently, Eisai has obtained approval for lenvatinib as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, and in Europe. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 35 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma.
Furthermore, in a Phase III clinical study (Study 304) comparing safety and efficacy of the agent versus sorafenib for the treatment of hepatocellular carcinoma, the agent achieved its primary endpoint of overall survival, meeting the statistical criteria for non-inferiority to sorafenib. Following the submission of applications in Japan (June 2017), the United States and Europe (July 2017), Eisai also plans to submit an application for lenvatinib for the treatment of hepatocellular carcinoma in China within the latter half of fiscal 2017.
Additionally, a Phase III clinical study (Study 307) of the agent in combination with either everolimus or pembrolizumab as a first line treatment for renal cell carcinoma is underway.
About Study 111
Study 111 is a multicenter, open-label Phase Ib/II clinical study being carried out in the United States to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab. The primary endpoint of the Phase Ib part was to determine the maximum tolerated dose. Thirteen patients with unresectable solid tumors (non-small cell lung cancer, renal cell carcinoma, endometrial cancer, urothelial cancer, head and neck cancer, and melanoma) who had progressed after treatment with approved therapies or for which there are no standard effective therapies available were administered 24 mg (3 patients) or 20 mg (10 patients) of lenvatinib orally daily, as well as 200 mg of pembrolizumab intravenously every three weeks. The Phase II part was conducted on patients with select solid tumors who had previously undergone less than 2 chemotherapy regimens, with a recommended dosage of 20 mg of lenvatinib daily and 200 mg of pembrolizumab every three weeks as determined based on the results of the Phase Ib part. The primary endpoint of the Phase II part was objective response rate at 24 weeks after treatment began, with secondary endpoints including objective response rate, disease control rate, progression-free survival, and duration of response. Currently, the Phase II part is underway, with enrollment expanded for the endometrial cancer cohort.
In addition, Phase Ib clinical studies of lenvatinib in combination with pembrolizumab for the treatment of select solid tumors (Study 115) and hepatocellular carcinoma (Study 116) are ongoing in Japan.
About research on mechanisms of action in combination of lenvatinib and anti-PD-1 antibody
In a non-clinical study where mouse models were inoculated with mouse liver cancer, melanoma or colon cancer cell lines and treated with a combinartion of lenvatinib with an anti-mouse PD-1 antibody, synergistic anti-tumor activities were demonstrated.4 These are thought to be a result of an immunostimulatory response through a reduction in immunosuppressive tumor-associated macrophages and an increase in cytotoxic T lymphocytes by lenvatinib.
(1) Lee CH, et al. A Phase 1b/2 Trial of Lenvatinib + Pembrolizumab in Patients With Renal Cell Carcinoma. ESMO Congress Abstract, 2017; #847O (2) GLOBOCAN2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/ (3) Eble J.N, et al. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, World Health Organisation classification of tumours. (International Agency for Research on Cancer, Lyon, France in 2004) (4) Kato Y, et al. Upregulation of memory T cell population and enhancement of Th1 response by lenvatinib potentiate anti-tumor activity of PD-1 signaling blockade : Lenvatineb and PD-1 mAb combination. AACR Meeting Abstract, 2017; #4614
Contact:Public Relations Department,
Eisai Co., Ltd.
+81-3-3817-5120
Source: Eisai Sectors: BioTech
Copyright ©2024 JCN Newswire. All rights reserved. A division of Japan Corporate News Network.
|
Latest Release
JCB enables JCB Contactless acceptance at Taichung MRT in Taiwan Apr 26, 2024 10:00 JST
| Mazda Production and Sales Results for March 2024 and for April 2023 through March 2024 Apr 25, 2024 18:21 JST
| MHI Begins Operation of SOEC Test Module the Next-Generation High-Efficiency Hydrogen Production Technology at Takasago Hydrogen Park Apr 25, 2024 17:45 JST
| GAC Honda to Begin Sales of All-new e:NP2, the Second Model of e:N Series Apr 25, 2024 16:50 JST
| Toyota Exhibiting at Beijing Motor Show 2024 Apr 25, 2024 16:25 JST
| Honda Reaches Basic Agreement with Asahi Kasei on Collaboration for Production of Battery Separators for Automotive Batteries in Canada Apr 25, 2024 11:10 JST
| UNIQLO Sponsors KAWS + Warhol Exhibition Tour, Starting in Pittsburgh Apr 25, 2024 09:00 JST
| Mitsubishi Power Begins Commercial Operation of Seventh M701JAC Gas Turbine in Thailand GTCC Project; Achieves 75,000 AOH To-Date Apr 24, 2024 17:19 JST
| MC and Denka Sign J/V Agreement in Fullerene Business Apr 24, 2024 17:02 JST
| Mitsubishi Motors Posts Record Sales in the Philippines in FY2023 Apr 24, 2024 13:56 JST
| NEC Develops High-speed Generative AI Large Language Models (LLM) with World-class Performance Apr 24, 2024 13:25 JST
| Fujitsu SX Survey reveals key success factors for sustainability Apr 23, 2024 10:25 JST
| Fujitsu and METRON collaborate to drive ESG success: slashing energy costs, boosting productivity with new manufacturing industry solutions Apr 22, 2024 16:09 JST
| NEC Strengthens Commitment to Space Industry with Investment in Seraphim Space Venture Fund II Apr 22, 2024 15:09 JST
| Soft Space Launches the First and Only JCB Payment Gateway in Malaysia Apr 22, 2024 15:00 JST
| TOYOTA GAZOO Racing takes a one-two in Croatian thriller Apr 22, 2024 10:47 JST
| First-ever Mazda CX-80 Crossover SUV Unveiled in Europe Apr 19, 2024 13:50 JST
| Fujitsu develops technology to convert corporate digital identity credentials, enabling participation of non-European companies in European data spaces Apr 19, 2024 10:17 JST
| Mitsubishi Heavy Industries and NGK to Jointly Develop Hydrogen Purification System from Ammonia Cracking Gas Apr 18, 2024 17:01 JST
| Toyota Launches All-New Land Cruiser "250" Series in Japan Apr 18, 2024 13:39 JST
|
More Latest Release >>
|