Tag: cancer treatment
Breaking News
LENVIMA in Combination with KEYTRUDA Approved In Taiwan for the Treatment of Patients with Advanced Endometrial Carcinoma
The approval is based on results from the pivotal Phase 3 Study 309/KEYNOTE-775 trial. These results were presented at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women's Cancer in March 2021, and published in the New England Journal of Medicine in January 2022.(1)
In this trial, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in overall survival (OS), reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001), and progression-free survival (PFS), reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), versus chemotherapy (investigator's choice of doxorubicin or paclitaxel). The median OS was 18.3 months for LENVIMA plus KEYTRUDA versus 11.4 months for chemotherapy. The median PFS was 7.2 months for LENVIMA plus KEYTRUDA versus 3.8 months for chemotherapy. The objective response rate (ORR) was 32% (95% CI, 27-37) for patients treated with LENVIMA plus KEYTRUDA versus 15% (95% CI, 11-18) for patients treated with chemotherapy (p<0.0001). Patients treated with LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 7% and partial response (PR) rate of 25% versus a CR rate of 3% and a PR rate of 12% for patients treated with chemotherapy.(2) In this trial, the five most common adverse reactions (any grade) observed in the LENVIMA plus KEYTRUDA combination arm were hypothyroidism, hypertension, fatigue, diarrhea and musculoskeletal disorders.(2)
LENVIMA plus KEYTRUDA was previously approved under accelerated approval process in Taiwan, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation based on data from the Study 111/KEYNOTE-146 trial. In accordance with accelerated approval regulations, continued approval was contingent upon verification and description of clinical benefit; these accelerated approval requirements have been fulfilled with the data from Study 309/KEYNOTE-775.
Endometrial cancer is the most common type of uterine body cancer. It is considered that more than 90% of uterine body cancers occur in the endometrium.(3) Worldwide, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers in 2020.(4) In Taiwan, there were more than 2,700 new cases of uterine body cancer and nearly 400 deaths from the disease in 2018.(5) The five-year relative survival rate for metastatic endometrial cancer (stage IV) is estimated to be approximately 17%.(6)
Eisai positions oncology as a key therapeutic area and is aiming to discover innovative new medicines with the potential to cure cancer. Eisai is committed to expanding the potential clinical benefits of lenvatinib for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals.
*In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy pembrolizumab from Merck & Co., Inc., Kenilworth, N.J., U.S.A.
About LENVIMA (lenvatinib mesylate)
LENVIMA, discovered and developed by Eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.
Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in the United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it has been approved in combination with KEYTRUDA as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. In Japan, it has been approved in combination with KEYTRUDA as the treatment of patients with unresectable advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy and with radically unresectable or metastatic renal cell carcinoma.
About Study 309/KEYNOTE-775 Trial
The approval was based on data from Study 309/KEYNOTE-775 (ClinicalTrials.gov, NCT03517449), a Phase 3 multicenter, open-label, randomized, active-controlled study conducted in 827 patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. The primary efficacy outcome measures were OS, and PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1.
Patients were randomized 1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks) or investigator's choice, consisting of either doxorubicin (60 mg/m2 every three weeks) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off). Treatment with LENVIMA plus KEYTRUDA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for KEYTRUDA, a maximum of 24 months. Administration of LENVIMA plus KEYTRUDA was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated.
About the Merck & Co., Inc., Kenilworth, N.J., U.S.A. and Eisai Strategic Collaboration
In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.
In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.
In Taiwan, Eisai's pharmaceutical sales subsidiary Eisai Taiwan Inc. is marketing Lenvima and is co-commercializing it with a local branch of Merck & Co., Inc., Kenilworth, N.J., U.S.A.
(1) V. Makker. et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.
The New England Journal of Medicine. bit.ly/3HPQ59b
(2) The information listed in Taiwanese Package insert
(3) American Cancer Society, "Causes, Risks, Prevention." Endometrial Cancer. bit.ly/3HNy6jy
(4) International Agency for Research on Cancer, World Health Organization. "Corpus uteri Fact Sheet." Cancer Today, 2020. bit.ly/35tT3TP
(5) Taiwan Cancer Registry 2018 Report.
(6) American Cancer Society, "Survival Rates for Endometrial Cancer." bit.ly/3hLZe8i
Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
Copyright 2022 JCN Newswire. All rights reserved. www.jcnnewswire.comEisai Co., Ltd. announced today that LENVIMA (generic name: lenvatinib mesylate), the multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.
Fujitsu and Tokyo Medical and Dental University leverage world’s fastest supercomputer and AI technology for scientific discovery to shed light on drug resistance in...
 |
Fujitsu and TMDU applied this technology to gene expression level(2) data obtained from cancer cell lines in order to analyze drug resistance(3) against anticancer drugs, and succeeded in extracting a new causal mechanism of a previously unknown gene that suggests a cause of resistance to lung cancer drugs. The new technology is expected to contribute to the acceleration of drug discovery and the realization of cancer therapies individualized for each patient.
The technology was developed under the theme of "elucidation of the cause and diversity of cancer using large-scale data analysis and AI technology," an initiative supported by TMDU, Kyoto University and Fujitsu as part of the supercomputer Fugaku achievement acceleration program(4).
Background
Even if a patient receives a targeted cancer drug(5) therapy, the appearance of drug-resistant cancer cells represents an ongoing threat to full remission. The mechanism for how certain cancers become drug resistant remains unclear, however, and researchers continue to work on new methods of analysis that shed light on how cells that have multiple driver mutations(6) acquire drug resistance. In drug development and clinical trials involving drug repositioning(7), it is important to identify patients for whom drugs are anticipated to have an effect. However, the effectiveness of drugs may differ depending on the organ and the individual and variations in gene expression, and the number of patterns combining expression levels of multiple genes exceeds 1,000 trillion(8). A comprehensive search of all 20,000 genes in the human genome would thus take more than 4,000 years with a conventional computer and finding ways to accelerate the process represents a major challenge.
Newly developed technology
Fujitsu implemented parallel conditional and causal algorithms to maximize computational performance with the supercomputer Fugaku to analyze the human genome within a timeframe needed for practical research. By utilizing Fujitsu's "Wide Learning"(9) AI technology to extract combinations of potential genes relating to the emergence of drug resistance based on statistical information, Fujitsu developed a novel technology that makes it possible to conduct a comprehensive search within a day.
Results
As a result of running data of the Dependency Map (DepMap)(10) portal using this technology on the supercomputer Fugaku, Fujitsu and TMDU were able to search the entire human genome for conditions and causality within a single day and determine the genes that cause resistance to drugs used to treat lung cancer(11).
Comment from Prof. Seiji Ogawa, Graduate School of Medicine, Kyoto University
Promising technologies like Fujitsu's AI technology for scientific discovery ("Wide Learning") may one day contribute to the discovery of biomarkers, which represent an area of growing interest in drug development. The key to the success of new drug development is to identify patients who are expected to benefit from new drugs and conduct clinical trials. If the marker that predicts who will benefit from the drug is known, the cost of clinical trials can significantly be reduced and the probability of success by conducting individual clinical trials can be increased. From this point of view, pharmaceutical manufacturers and others are expected to be very interested in this technology. The fact that it has been implemented using Fugaku has also raised expectations.
Future Plans
Moving forward, Fujitsu and TMDU will conduct a multilayered and comprehensive analysis that combines various data including time axis and location data with the aim of accelerating medical research, including in the field of drug efficacy, as well as to shed light on the causes of cancer.
Fujitsu and TMDU will also collaborate in experimental research in the fields of drug discovery and medicine. TMDU will further utilize the technology developed in this research to promote research on strategies for intractable diseases such as cancer.
In addition to medical care, Fujitsu will utilize the new technology to resolve challenges in a variety of fields, including marketing, system operations and manufacturing.
Acknowledgements
This research was conducted as part of Ministry of Education, Culture, Sports, Science and Technology's Fugaku Achievement Acceleration Program "Understanding the Origin and Diversity of Cancer through Large-scale Data Analysis and Artificial Intelligence Technologies" (JPMXP 1020200102). A part of the research was conducted with the computational resources of supercomputer Fugaku (Issue #: hp 200138, hp 210167).
(1) Supercomputer "Fugaku":
A computer installed at RIKEN as a successor to the supercomputer "K." From June 2020 to November 3, it ranked first in 4 categories in the supercomputer rankings for 4 consecutive years. Full operation started on March 9, 2021.
(2) Gene expression level :
Amount of RNA copied from DNA (the same nucleic acid as DNA synthesized by transcription using some DNA sequences as templates).
(3) Drug resistance :
A phenomenon in which the effect of a drug weakens while the drug is being administered.
(4) Supercomputer Fugaku Achievement Acceleration Program :
Program started in May 2020 by the Ministry of Education, Culture, Sports, Science and Technology with the aim to achieve early results.
(5) Targeted drug :
A drug designed to act only on the molecule (protein, gene, etc.) that is causing the disease.
(6) Driver mutations :
A genetic mutation that directly causes the development or progression of cancer.
(7) Drug repositioning :
The application of existing drugs developed and approved for the treatment of one disease to the treatment of another disease.
(8) More than 1,000 trillion :
Even if the expression level of each gene is restricted to a combination of 50 major genes known to be related to cancer and the expression level of each gene is classified into 2 categories (e.g., "high" or "low" gene expression), the condition number is 2 to the power of 50, which exceeds 1,000 trillion.
(9) Wide Learning :
Official site "Hello, Wide Learning!"
(10) Dependency Map (DepMap) :
Data on the sensitivity and resistance of approximately 4,500 drugs to approximately 600 different cancer cell lines, provided by the American Broad Institute. Mutation information of cancer cell lines and expression data of all genes are included.
(11) Fujitsu and TMDU analyzed gene expression data from DepMap of approximately 300 cancer cell lines, sensitivity and resistance data of Gefitinib (molecularly targeted drug used to treat lung cancer and other cancer types), and comprehensively searched for conditions and mechanisms of cancer cell lines that do not respond to Gefitinib. Fujitsu and TMDU identified conditions under which the expression levels of three transcription factors (genes that control gene transcription (synthesis of RNA)), ZNF516, E2F6, and EMX1, were low. In lung cancer cell lines that meet these conditions, a mechanism triggered by the transcription factors SP7 and PRRX1 was discovered as further potential causes of drug resistance in cancer cells (see reference image).
About Fujitsu
Fujitsu is the leading Japanese information and communication technology (ICT) company offering a full range of technology products, solutions and services. Approximately 126,000 Fujitsu people support customers in more than 100 countries. We use our experience and the power of ICT to shape the future of society with our customers. Fujitsu Limited (TSE:6702) reported consolidated revenues of 3.6 trillion yen (US$34 billion) for the fiscal year ended March 31, 2021. For more information, please see www.fujitsu.com.
About Tokyo Medical and Dental University
Tokyo Medical and Dental University (TMDU) is Japan's only comprehensive medical university and graduate school, and has provided advanced medical treatment through a fusion of the medical and dental fields and worked to cultivate "professionals with knowledge and humanity." TMDU contributes to human health and the well-being of society by fostering outstanding healthcare professionals with a humane and global outlook.
Copyright 2022 JCN Newswire. All rights reserved. www.jcnnewswire.comFujitsu and the Tokyo Medical and Dental University (TMDU) today announced a new technology that uses AI to discover new causal mechanisms of drug resistance in cancer treatments from clinical data.
Latest Intelligence
