News Article | June 4, 2017
The REFLECT study (Study 304) is the first non-inferiority trial to show statistically significant results for a systemic therapy versus the current standard of care in uHCC, also demonstrating improvements in the secondary endpoints of progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). Hepatocellular carcinoma (HCC) is a complex disease associated with a poor prognosis and accounts for approximately 90% of liver cancer cases worldwide. The incidence of liver cancer in Europe has been rising steadily over the past decade. uHCC is an advanced hard-to-treat stage of liver cancer that affects >70% of patients. HCC is the second most common cause of death from cancer worldwide, estimated to be responsible for nearly 746,000 deaths across the globe in 2012. In Europe an estimated 71,000 people were diagnosed with liver cancer and 69,000 people died from this disease in 2012. "Results from this large Phase III trial demonstrate the potential of lenvatinib to improve the outcomes of liver cancer patients, and provide an overall survival benefit that is non-inferior to sorafenib, currently the only systemic therapy approved by the European Medicines Agency for unresectable HCC," commented Professor Jeff Evans, Professor of Translational Cancer Research, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow and investigator of the study. "For a decade there has been no advance in the first-line systemic treatment of uHCC in Europe, so this data supports a potential new option for liver cancer patients that offers greater choice." REFLECT is a Phase III open label non-inferiority study to compare the efficacy and safety of lenvatinib (n=478) versus sorafenib (n=476) as a first-line systemic treatment in patients with uHCC. The median OS for patients treated with lenvatinib was 13.6 months (95% CI: 12.1 - 14.9 months) compared to 12.3 months (95% CI: 10.4 - 13.9 months) for sorafenib (HR: 0.92; 95% CI: 0.79 - 1.06). Median PFS was 7.4 months (95% CI: 6.9-8.8 months) with lenvatinib with a median TTP of 8.9 months (95% CI; 7.4-9.2 months) compared to median PFS of 3.7 months (95% CI: 3.6-4.6 months) (HR: 0.66; 95% CI: 0.57 - 0.77; p<0.00001) and median TTP of 3.7 months on sorafenib (95% CI; 3.6-5.4 months) (HR 0.63; 95% CI; 0.53 - 0.73; p<0.00001). In addition, lenvatinib demonstrated significantly higher ORR (24%) compared to sorafenib (9%) (odds ratio: 3.13; 95% CI: 2.15-4.56; p<0.00001). ORR was evaluated using mRECIST. The most common treatment-emergent adverse events (TEAEs) of any grade among patients who received lenvatinib were hypertension (42.2%), diarrhoea (38.7%), decreased appetite (34.0%), and decreased weight (30.9%). In the sorafenib arm, the most common TEAEs were palmar-plantar erythrodysesthaesia (hand-foot syndrome) (52.4%), diarrhoea (46.3%), hypertension (30.3%), and decreased appetite (26.3%). TEAEs occurred in 98.7% of patients in the lenvatinib arm and 99.4% in the sorafenib arm of the study. "Lenvatinib is already indicated for the treatment of radioiodine refractory differentiated thyroid cancer and advanced renal cell carcinoma, and continues to show compelling results in difficult-to-treat cancers. Eisai is excited by the potential of the results seen with lenvatinib in Study 304 to provide improved outcomes for patients with unresectable HCC, who face a poor prognosis and are in need of additional treatment options," said Gary Hendler, Chairman & CEO EMEA, Chief Commercial Officer, Oncology Business Group at Eisai. "Based on these data, Eisai plans to submit regulatory applications for lenvatinib for the first-line treatment of patients with unresectable HCC and we look forward to working closely with the European Medicines Agency and other regulatory bodies worldwide." Eisai is dedicated to the discovery, development and production of innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives to better understand the needs of patients and their families to increase the benefits health care provides. REFLECT is an international, multicentre, randomised, open-label, non-inferiority Phase III study to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in patients with uHCC. Patients (n=954) at 183 trial sites in 21 countries were randomised to receive lenvatinib 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was overall survival. The secondary efficacy endpoints of this study were progression-free survival, time to progression and objective response rate. Lenvatinib, discovered and developed by Eisai, is an oral multikinase inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes., Lenvima® (lenvatinib) is approved in the EU and the US for specific patient populations: In the European Union lenvatinib is indicated: About Eisai Co., Ltd. Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Oncology and Neurology. As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries. For more information about Eisai Co., Ltd., please visit www.eisai.com. 1. Cheng A, et al. Phase 3 trial of lenvatinib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC). American Society for Clinical Oncology annual meeting 2017; Abstract No. 4001 2. Weledj E, et al. How grim is hepatocellular carcinoma? Annals of Medicine & Surgery 2014; 3(3):71-76 3. McGlynn KA, et al. The Global Epidemiology of Hepatocellular Carcinoma, Present and Future. Clin Liver Dis 2011; 15(2):223-243 4. Lencioni R, et al. Treatment of Intermediate/Advanced Hepatocellular Carcinoma in the Clinic: How Can Outcomes Be Improved? The Oncologist 2010;15:42-52 5. World Health Organization. Estimated Incidence, Mortality and Prevalence Worldwide in 2012. GLOBOCAN Cancer Fact Sheets: Liver Cancer. Available at: http://gco.iarc.fr/today/data/pdf/fact-sheets/cancers/cancer-fact-sheets-7.pdf Accessed May 2017. 6. Matsui J, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 2008;122:664-671. 7. Okamoto K, et al. Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization. ACS Medicinal Chemistry Letter 2010.
News Article | June 1, 2017
SCOTTSDALE, AZ--(Marketwired - Jun 1, 2017) - KEY CAPITAL CORPORATION ( : KCPC) advises the Company is progressing partnerships with established and recognized medical professionals and facilities within its Guatemala and Costa Rica licensed territories with an initial focus on liver cancer treatment options. Further, that Dr. Steve Kramer from Fort Collins, Colorado, one of 75 patients in a study reported in open access Journal of Hepatocellular Carcinoma, has independently released a YouTube testimonial of appreciation and support more than two and a half years after commencement of his successful Hepko-V5 treatment resulting in Complete Remission. For Reference See: https://www.dovepress.com/articles.php?article_id=32377, and https://www.youtube.com/watch?v=yrlgnO8WFjM Following the reported success of the open-label Phase II study of Hepko-V5 oral immunotherapeutic vaccine conducted in 75 patients with late stage hepatocellular carcinoma (HCC), Hepko-V5 is now in Phase III trial stage. Based on encouraging preliminary data, Hepko-V5 has received orphan drug designation from the U.S. Food and Drug Administration (FDA), which clears the path toward approval in U.S.A. market, and a Phase II trial in patients with cholangiocarcinoma -- the second most common form of liver cancer affecting bile ducts -- has been initiated. Additionally, our Licensor last week announced the Phase II, open-label, immunotherapy trial in patients with pancreatic cancer (See registration NCT03165591) that will seek to engage at least 30 patients with inoperable and chemotherapy-failed pancreatic cancer for a 3-month trial. The main inclusion criteria are higher than normal baseline levels of CA 19.9 tumor antigen. Key Capital believes the planned pancreatic cancer trial will prove as groundbreaking as the Hepko-V5 Immunotherapy demonstrated in cases of advanced and terminal liver cancer. For further information: See www.keycapitalgroup.com Disclaimer: Statements made in this press release that express the Company or management's intentions, plans, beliefs, expectations, or predictions of future events, are forward-looking statements. The words "believe," "expect," "intend," "estimate," "anticipate," "will" and similar expressions are intended to further identify such forward-looking statements, although not all forward-looking statements contain these identifying words. Those statements are based on many assumptions and are subject to many known and unknown risks, uncertainties and other factors that could cause the Company's actual activities, results or performance to differ materially from those anticipated or projected in such forward-looking statements. The Company cannot guarantee future financial results, levels of activity, performance or achievements and investors should not place undue reliance on the Company's forward-looking statements.
News Article | June 3, 2017
BURLINGTON, Mass.--(BUSINESS WIRE)--ArQule, Inc. (Nasdaq: ARQL) today announced that data from a phase 1/2 trial with fibroblast growth factor receptor (FGFR) inhibitor, ARQ 087, presented at ASCO demonstrate a meaningful clinical benefit to intrahepatic cholangiocarcinoma (iCCA) patients harboring FGFR2 fusions. The data show a robust response rate and prolonged duration of therapy for these patients well in excess of that reported for second-line chemotherapy. These data support future development of ARQ 087 as second-line treatment, and a registrational phase 3 trial in iCCA FGFR2 fusion positive patients is planned to begin in the third quarter of 2017. ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family. The presentation titled “ARQ 087, an oral pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor, in patients with advanced intrahepatic cholangiocarcinoma (iCCA) with FGFR2 genetic aberrations” can be viewed at https://www.arqule.com/wp-content/uploads/ARQ-087-101_Poster_ASCO-2017.pdf. “Clinical evidence is accumulating on the role of FGFR inhibitors in cholangiocarcinoma and other FGFR driven tumors such as urothelial and gastric cancers,” said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. “We are encouraged to see that both the response rate and disease control rate were consistent throughout the trial. Patients with iCCA often have a poor prognosis for front-line treatment with chemotherapy, and there are no currently approved second-line therapeutic options.” Patients with advanced iCCA who relapse after first-line multi-agent chemotherapy have limited treatment options with poor prognosis. In recent years, FGFR2 fusions have been recognized as a potential iCCA-specific therapeutic target. The company has been granted orphan drug designation by the U.S. Food and Drug Administration and European Medicines Agency for ARQ 087 in this indication. Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC)1. Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. The average age adjusted incidence rate for iCCA is approximately one in 100,000 per year in the United States and Europe2,3. ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (“FGFR”) family with demonstrated efficacy in FGFR2 genetic alterations. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. ARQ 087 has demonstrated in vivo inhibition of tumor growth and downstream signaling in tumors whose growth is driven by FGFR. Signals of single agent activity with this drug were observed in phase 1a testing. Phase 1b expansion cohorts with ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplifications and mutations. Clinical development of ARQ 087 advanced into phase 2 for intrahepatic cholangiocarcinoma (iCCA) in patients with FGFR2 fusions following the observation of two confirmed responses in this patient population in the phase 1 portion of the program, and a phase 3 registrational trial is planned to begin in the third quarter of 2017 in this same patient population. ArQule is a biopharmaceutical company engaged in the research and development of targeted therapeutics to treat cancers and rare diseases. ArQule’s mission is to discover, develop and commercialize novel small molecule drugs in areas of high unmet need that will dramatically extend and improve the lives of our patients. Our clinical-stage pipeline consists of four drug candidates, all of which are in targeted, biomarker-defined patient populations, making ArQule a leader among companies our size in precision medicine. ArQule’s proprietary pipeline includes: ARQ 087, a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family, in phase 2 for iCCA and in phase 1b for multiple oncology indications; ARQ 092, a selective inhibitor of the AKT serine/threonine kinase, in phase 1/2 company sponsored study for Overgrowth Diseases, in phase 1 for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH), as well as in multiple oncology indications; ARQ 751, a next generation AKT inhibitor, in phase 1 for patients with AKT1 and PI3K mutations; and ARQ 761, a β-lapachone analog being evaluated as a promoter of NQO1-mediated programmed cancer cell necrosis, in phase 1/2 in multiple oncology indications in partnership with the University of Texas Southwestern Medical Center. In addition, we have advanced ARQ 531, an investigational, orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant BTK, through toxicology testing and plan to initiate a phase 1 trial by the third quarter of 2017. ArQule’s current discovery efforts are focused on the identification and development of novel kinase inhibitors, leveraging the Company’s proprietary library of compounds. You can follow us on Twitter and LinkedIn. This press release contains forward-looking statements regarding the Company’s clinical trials with ARQ 087. These statements are based on the Company’s current beliefs and expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. Positive information about pre-clinical and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 087 may not demonstrate promising therapeutic effect; in addition, these drugs may not demonstrate appropriate safety profiles in current or later stage or larger scale clinical trials as a result of known or as yet unanticipated side effects. The results achieved in later stage trials may not be sufficient to meet applicable regulatory standards or to justify further development. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing these compounds that could lead the Company to discontinue development. Even if later stage clinical trials are successful, unexpected concerns may arise from subsequent analysis of data or from additional data. Obstacles may arise or issues may be identified in connection with review of clinical data with regulatory authorities. Regulatory authorities may disagree with the Company’s view of the data or require additional data or information or additional studies. In addition, we plan to develop and use a companion diagnostic to identify patients with FGFR2 and possibly other fusions for our future ARQ 087 clinical trials. We intend to outsource the development of such companion diagnostics to one or more third party collaborators. There can be no assurance that we will successfully enter into an agreement or agreements with any such collaborators; in addition, any such collaborator may encounter difficulties in developing and obtaining approval for such companion diagnostic, including issues relating to selectivity/specificity, analytical validation, reproducibility, concordance or clinical validation. Any delay or failure to develop or obtain regulatory approval of such companion diagnostic could delay or prevent approval of ARQ 087. Drug development involves a high degree of risk. Only a small number of research and development programs result in the commercialization of a product. Furthermore, ArQule may not have the financial or human resources to successfully pursue drug discovery in the future. For more detailed information on the risks and uncertainties associated with the Company’s drug development and other activities, see the Company’s periodic reports filed with the Securities and Exchange Commission. The Company does not undertake any obligation to publicly update any forward-looking statements. 1 Welzel TM, et al. Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst. 2006; 98(12),873–875. 2 National Cancer Institute: Surveillance, Epidemiology, and End Results 3 rarecarenet.eu
Hcc Inc. | Date: 2016-11-22
A hydraulic system for driving a post driver of a skid steer loader. The hydraulic system includes a master cylinder disposed between a valve, such as a 4-way valve, and the driver cylinder of the post driver. The master cylinder effectively provides that hydraulic fluid from the 4-way valve to the hydraulic system of the skid steer loader can flow freely without needing an auxiliary pump and motor to overcome resistance in the return line back to the skid steer loader hydraulic system. By eliminating the restriction in the return line of the driver cylinder, a very fast retraction can be achieved, improving the impact performance of the system.
HCC Inc. | Date: 2016-08-30
A cam follower design wherein a cam track is provided proximate one or both ends of a harvester pick-up reel. Cam followers travel along the cam track as the pick-up reel rotates to move crop into the harvester. At least one roller of each cam follower engages and rolls along an interior edge surface of the cam track, and at least one other roller of each cam follower engages and rolls along an exterior edge surface of the cam track. The rollers are preferably engaged with a carrier member which is linked to a corresponding bat tube. Each cam follower preferably also includes at least one over center stop which is configured to maintain the intended radial position of the bat tube.
Hcc Inc. | Date: 2016-08-01
A non-split bearing design for use with a harvester pick-up reel. In one specific embodiment, the outer member directly engages the inner member. In another embodiment, the bearing is provided as being an interchangeable roller bearing, and in that case there is preferably an intermediate member which is disposed between the outer member and the inner member. Regardless, providing that the bearing is non-split provides that the design is simplified, as well as provides that the inner bore, i.e., the bore which engages the bat tube, can be more easily controlled, thereby reducing or even eliminating service requirements.
Hcc Inc. | Date: 2016-06-28
A tool or extractor which is lightweight and portable. The tool includes a plate which is mountable to a mini-skid steer loader. The tool includes a first jaw member which is fixed. The first jaw member is preferably welded or otherwise attached to or engaged with the plate. The tool also includes a second jaw member. The second jaw member is moveable, such as via a hydraulic cylinder, and is pivotably connected the plate. The hydraulic cylinder is also preferably pivotably connected to the plate, and is controlled in order to affect a grip on a thing to be extracted. The mini-skid steer loader is then operable to pull up on the thing, and extract the thing from the ground.
HCC Inc. | Date: 2015-10-13
A tine for use with a harvester. The tine is preferably an injection molded polymer pickup reel tine, which uses a front-to-rear mold parting line direction. The tine preferably has a snap ring or strap portion which is configured to engage a bat tube, as well as a finger portion which is configured to engage the crop during harvesting. Preferably, the front-to-rear parting line is along both portions. The front-to-rear parting line allows for the ability to provide a deep front-to-rear cross section for rigidity at the high stress area of the tine. Two front-to-rear material saving features can be utilized to minimize material usage and allow for relative consistent wall thickness, which results in a rigid cross section that maintains deflection stability in the normal direction of deflection. The preferred form of the tine cross section includes three deep oval sections or projections, connected by two oval depressions, but other variations are entirely possible while still resulting in effectively the same benefits.
HCC Inc. | Date: 2015-11-03
A roller frame assembly for a pick-up reel of a harvester, where the roller frame assembly is adjustable in that its position can be easily adjusted relative to a position of a drive shaft of the pick-up reel, thereby effectively converting the pick-up reel from a flip reel to a non-flip reel, and vice versa.
Hcc Inc. | Date: 2016-02-03
A bat tube for use with a harvester pick-up reel. The bat tube is configured to resist torsional loads, without having to use fasteners that engage holes in the bat tube. Preferably, the external surface of the bat tube provides at least one key or keyway that engages a corresponding keyway or key in the band or strap portion of the tines. As such, once a tine is engaged with the bat tube, the tine is generally prevented from rotating about the bat tube. Additionally, by not using fasteners to engage holes in the bat tube, spacing between the tines can be varied. The bat tube allows for tine fastening and torsional resistance without drilling or punching holes, which allows for easily variable tine spacings. It also allows for improved crop gathering and crop entry characteristics over a typical round profile.