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Uzan C.,Gustave Roussy
Human reproduction (Oxford, England) | Year: 2013

Here we report the outcomes of 26 patients who relapsed following conservative surgical treatment of stage I serous borderline ovarian tumours treated initially with fertility-sparing surgery. All recurrences were diagnosed by systematic ultrasonography during follow-up. Eleven patients relapsed at least twice after such management. Twenty-one pregnancies were observed in 13 patients. Eleven of these patients became pregnant after the treatment of their first recurrence. All patients had a borderline ovarian tumour and/or non-invasive peritoneal implants at the time of the first recurrence but two of them had invasive ovarian and peritoneal disease at the time of the second or third recurrence (one of them died of disease). Fertility-preserving surgery remains a valuable alternative (if technically feasible), in young patients with recurrent SBOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy. However, it should be associated with meticulous follow-up because the risk of progression to carcinoma exists, albeit small.


News Article | December 1, 2016
Site: www.eurekalert.org

Munich, Germany: Researchers working to find effective treatments for soft tissue sarcomas have discovered that combining a new anti-cancer drug with an existing one kills cancer cells not only in the laboratory but also in the first two patients treated with it, leading to unusually long-lasting periods without the disease progressing. Soft tissue sarcomas - cancers of soft tissues such as fat, muscles, blood vessels, nerves, tendons and ligaments - are rare but difficult to treat successfully if they are advanced and have spread to other parts of the body (metastasised). In a late-breaking presentation at the 28th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany, today (Friday), Professor Antoine Italiano, head of the Early Phase Trials and Sarcoma Units at Institut Bergonié, Bordeaux, France, described how a new drug, GDC-0575, inhibits a molecule called Checkpoint kinase 1 (CHK1) that regulates the response of cancer cells to DNA damage. By inhibiting CHK1, the drug prevents tumour cells recovering from DNA damage and they die. Combining GDC-0575 with gemcitabine, a cancer-killing drug that is already used for treating sarcomas, proved remarkably effective. "Soft tissue sarcomas represent a rare group of malignant tumours. Despite the use of surgery, radiotherapy and chemotherapy to treat the tumour in the localised region in which it started, up to 40% of patients will develop recurrence with cancer cells spreading to other parts of the body," he said. "The number of drugs approved to manage patients with advanced sarcoma is very low and patients in this setting have a very poor outcome with a median [average] overall survival of only 12-18 months. Gemcitabine is one of the drugs used in patients with advanced soft tissue sarcoma. "We did this study in order to assess if combining a CHK1 inhibitor with gemcitabine can improve the anti-tumour efficacy in pre-clinical models of the disease. We observed a very strong synergy between the CHK1 inhibitor GDC-0575 and gemcitabine in sarcoma cells in the lab, but also in mice. The combination of the two drugs significantly reduced tumour growth rate in comparison to treatment with just one drug both in the lab and in the mice. "Interestingly, two patients, who were treated with such a combination in a phase I clinical trial [3] had a meaningful response, which is quite unusual in this setting. Despite a significantly lower dose of gemcitabine than is used routinely, the tumours in these patients shrank rapidly and substantially for an unusually long-lasting time. The first patient who had a leiomyosarcoma [2] with extensive metastases in the peritoneum had a partial response, in which the tumour shrank, that lasted for one year. The second patient, who had lung metastases, had a complete response, in which the cancer completely disappeared, that is still ongoing nine months after the start of treatment." The patients had been given 250mg/m3 a week of gemcitabine instead of the more usual 660 mg/m3. Gemcitabine was given intravenously and GDC-0575 was given orally with a range of different doses. The researchers analysed tumour samples taken from the first patient at the start of treatment and when the cancer started to grow again to identify genes that might play a role in the patient's eventual resistance to the treatment. "We have identified 16 potential genes and these data now have to be validated by further studies," said Prof Italiano. The study is no longer enrolling new patients but Prof Italiano said: "Based on these pre-clinical and preliminary clinical data we will try to set up a phase II clinical trial to assess the safety and efficacy of gemcitabine plus a CHK1 inhibitor in soft-tissue sarcoma." Chair of the scientific committee for the Symposium, Professor Jean Charles Soria from the Institut Gustave Roussy (France), commented: "Exceptional responders in the clinical setting represent unique opportunities to better understand the biological basis underlying tumour shrinkage. This is very well exemplified in this work, where not only the basis of response is analysed by sequencing all the active genes in the tumour samples, but also the basis of acquired secondary resistance." [1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research]. [2] Leiomyosarcoma is one of the more common types of soft tissue sarcomas to develop in adults. [3] Clinical trial no: NCT01564251. "A study of GDC-0575 alone and in combination with gemcitabine in patients with refractory solid tumours or lymphoma".


VIENNE, AUTRICHE--(Marketwired - 8 décembre 2016) - Le point-presse d'aujourd'hui à l'occasion de la 17e Conférence mondiale sur le cancer du poumon (WCLC) de l'IASLC s'est concentré sur des essais cliniques qui font progresser le traitement du cancer du poumon grâce à l'immunothérapie et à de meilleurs diagnostics. Des résumés et des versions complètes des communiqués de presse pour chaque thème couvert sont disponibles via les liens fournis dans ce résumé, ou auprès de Chris Martin, représentant de l'IASLC auprès des médias, à l'adresse : cmartin@davidjamesgroup.com. Des chercheurs français présentent les résultats d'une étude d'harmonisation sur les tests d'immunohistochimie PD-L1 chez les patients atteints d'un cancer du poumon non à petites cellules (NSCLC). L'immunohistochimie (IHC) PD-L1 est considérée comme un biomarqueur prédictif pour la plupart des thérapies anti-PD-1/PDL-1 chez les patients atteints d'un cancer du poumon non à petites cellules, mais différents tests sont utilisés dans les essais cliniques. Les chercheurs en immunologie s'efforcent à trouver un test capable de prédire le statut PD-L1 de manière précise et cohérente, afin que les pathologistes et médecins soient en mesure d'identifier les patients pouvant bénéficier de l'immunothérapie. Des chercheurs français ont exposé aujourd'hui des données sur l'efficacité de plusieurs tests développés en laboratoire en comparaison avec les tests PD-L1 utilisés dans les essais cliniques. Ces données ont été présentées par le Dr Julien Adam du Centre de lutte contre le cancer Gustave Roussy, en France. Pour consulter le communiqué de presse dans son intégralité, cliquez ici. Le durvalumab est cliniquement actif et bien toléré chez les patients métastatiques ayant précédemment reçu de lourds traitements atteints de NSCLC. Le durvalumab est un anticorps monoclonal qui cible le PD-L1 (programmed death ligand 1). Il fait actuellement l'objet de tests en tant que monothérapie et en combinaison avec le tremelimumab (CTLA-4 mAb) chez les patients atteints de NSCLC. Le Dr Marina Garassino de la Fondazione IRCCS Istituto Nazionale dei Tumori, à Milan, a présenté aujourd'hui les données d'un essai mondial à un volet de phase II qui montrent que le durvalumab est cliniquement actif et bien toléré chez les patients métastatiques ayant précédemment reçu de lourds traitements atteints d'un cancer du poumon non à petites cellules (NSCLC). Pour lire le communiqué de presse dans son intégralité, cliquez ici. Les patients recevant du pembrolizumab bénéficient d'une meilleure qualité de vie que ceux traités par chimiothérapie. D'après des données présentées par le Dr Julie Brahmer du Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (États-Unis, les patients dans le volet pembrolizumab de l'essai KEYNOTE-024 ont enregistré une meilleure qualité de vie que ceux traités par chimiothérapie. Le pembrolizumab a été approuvé en octobre par la Food and Drug Administration pour le traitement des patients atteints d'un cancer du poumon non à petites cellules dont la maladie a progressé pendant ou après une chimiothérapie. Les données précédentes de l'essai KEYNOTE-024 ont démontré que le pembrolizumab fournit une survie sans progression supérieure et une meilleure survie globale en comparaison avec la chimiothérapie en tant que thérapie de première intention, chez les patients atteints de cancer du poumon non à petites cellules avancé présentant l'expression PD-L1 sur plus de 50 % des cellules tumorales et non sensibilisantes aux aberrations EGFR ou ALK. Lisez l'intégralité du communiqué de presse ici. Le nivolumab affiche des résultats prometteurs pour le traitement du mésothéliome pleural malin. L'immunothérapie nivolumab s'est montré prometteuse chez des patients atteints de mésothéliome pleural malin, d'après une étude présentée par le Dr Paul Baas de l'Institut du cancer des Pays-Bas à Amsterdam. Le mésothéliome pleural est un cancer de l'enveloppe protectrice du poumon (plèvre). Il est provoqué par l'inhalation de fibres d'amiante dans les poumons et représente la forme la plus courante de mésothéliome. " Le nivolumab en traitement de deuxième intention ou ultérieure chez les patients atteints de mésothéliome pleural malin récurrent malignant pleural mesothelioma a satisfaisait au critère principal, a déclaré le Dr Baas. Nous avons détecté une toxicité modérée et des résultats durables, et nous avons observé une corrélation claire entre l'expression PD-L1 et la réponse. " Pour en savoir plus, cliquez ici. L'essai OAK soutient l'utilisation de l'atezolizumab chez les patients atteints de NSCLC. Les patients ayant reçu de l'atezolizumab dans le cadre de l'essai OAK ont enregistré, en moyenne, une amélioration de 4,2 mois de la survie globale comparativement aux patients recrutés dans le volet docetaxel de l'essai, d'après des données présentées par le Dr Shirish Gadgeel du Karmanos Cancer Institute de l'université de Wayne State, à Détroit. Les résultats de l'analyse des sous-groupes ont démontré que l'atezolizumab avait amélioré la survie globale indépendamment de l'histologie et du statut PD-L1, mesuré par l'expression des gènes tumoraux ou par immunohistochimie IHC. Pour lire le communiqué dans son intégralité, cliquez ici. À propos de la WCLC : La WCLC est le plus important colloque au monde dédié au cancer du poumon et aux autres tumeurs thoraciques, réunissant plus de 6 000 chercheurs, médecins et spécialistes venus de plus de 100 pays. Son objectif est d'accroître la sensibilisation et de renforcer la collaboration et la compréhension du cancer du poumon, et d'aider les participants à mettre en œuvre les derniers développements partout dans le monde. Organisée sous le thème " Ensemble contre le cancer du poumon ", la conférence couvrira une vaste gamme de disciplines et dévoilera les résultats de plusieurs essais cliniques et études de recherche. Pour tout complément d'information, veuillez consulter le site http://wclc2016.iaslc.org/. L'Association internationale pour l'étude du cancer du poumon (IASLC) est la seule organisation mondiale qui se consacre à l'étude du cancer du poumon. Fondée en 1974, l'association compte parmi ses membres plus de 5 000 spécialistes du cancer du poumon issus de plus de 100 pays. Pour en savoir plus, rendez-vous à l'adresse www.iaslc.org.


News Article | September 14, 2016
Site: www.nature.com

Kidney cancer has frustrated the best efforts of clinicians. The disease is notoriously resistant to chemotherapy, and is often caught only after it has metastasized. As recently as 2013, survival for people with advanced cancer who were treated in clinical trials was two and a half years on average. “I've been here taking care of people with kidney cancer for over 25 years,” says Robert Motzer, a medical oncologist at the Memorial Sloan Kettering Cancer Center in New York City. “When I started here in the 1980s, the average survival on chemotherapy was less than a year. Treatment advances were modest over the intervening decades. But in the past year, three new drugs have brought hope. These therapies represent the “first big revolution that is going to change survival and the way we are going to treat our patients”, says Bernard Escudier, a kidney-cancer specialist at Gustave Roussy near Paris. The key developments revolve around research on the genetic changes that allow kidney tumours to create their own blood supply and grow. The new drugs target the specific pathways in the process, and hold promise for personalized therapy that is more effective, and has fewer side effects, than previous treatments. “The paradigm has changed with these new drugs all coming in within a year,” says Motzer. But it is a revolution that seems to have passed by early-stage kidney cancer. Targeted therapies do not prevent initial tumours from recurring and can have serious toxic effects. This 'good news, bad news' story, however, is teaching researchers more about how the disease works. Targeted therapy arose from the discovery that a gene called VHL is inactivated in most people with clear-cell renal cell carcinoma (RCC), which accounts for about 70% of kidney cancers. When it is functioning, VHL suppresses tumours by regulating angiogenesis — the formation of new blood vessels. Tumours need their own blood supply to grow, the loss of VHL allows this angiogenesis. Researchers have been exploring the promise of drugs that treat cancer by stopping angiogenesis since the process was first proposed in 1971 by the US vascular researcher Judah Folkman. The first antiangiogenesis drug for any type of cancer, bevacizumab, was approved in 2004 for metastatic colon cancer. The drug has since been approved for a variety of cancers, including advanced RCC. The first antiangiogenesis drugs approved specifically for RCC, sorafenib and sunitinib, were approved in 2005 and 2006. “It changed the way we treated this disease, away from chemotherapy and towards these targeted drugs,” says Motzer. “It opened up a whole new era of treatment.” Sorafenib and sunitinib opened the floodgates. In the next ten years came pazopanib and axitinib (see 'A new era of treatment'). Each of these drugs targets the tyrosine kinase receptors of an enzyme involved in the growth of blood vessels, vascular endothelial growth factor receptors (VEGFRs). In spring 2016, two more VEGFR inhibitors, cabozantinib and lenvatinib (in combination with everolimus), were approved by the US Food and Drug Administration (FDA) for the treatment of RCC. These newly approved drugs are more effective than their predecessors, increasing the time before the cancer progresses as well as improving survival. This might be because the drugs target other pathways in addition to VEGFR, says Motzer. Another new class of drug targets a different enzyme linked to angiogenesis, known as mTOR. Temsirolimus and everolimus were approved for advanced RCC by the FDA in 2007 and 2009, respectively. A third pathway involves a molecule made by many types of cancer cell: the ligand PD-L1 binds to a receptor called PD-1 on immune cells known as T cells and stops these cells from attacking the cancer. Nivolumab was approved for advanced RCC in November 2015. The checkpoint inhibitor blocks PD-1 on T cells, allowing the cells to find and kill the tumour (see page S109). Until the past-year's entrants on the scene, this plethora of new drugs had positive, but mixed, results. Motzer has led randomized trials of several of these drugs, and found that survival generally improved. Pazopanib and sunitinib increased average survival time to two and a half years1. “Patients have their disease controlled for a certain time period and then generally progress,” Motzer says. “We see very few complete remissions.” The outcomes have disappointed Naomi Haas, who specializes in kidney and prostate cancer at the University of Pennsylvania's Abramson Cancer Center in Philadelphia. The initial rush of excitement following the drugs' approvals has faded, she says. “As time went on, we realized the drugs had a lot of side effects and it was a small proportion of people who had complete disappearance of their cancer. And the drugs do not work for early-stage tumours. If RCC is caught before it has spread beyond the kidney, the survival rate is very high. Unfortunately, because early-stage tumours rarely cause pain or significant bleeding, they are usually found by accident, after diagnostic imaging for other reasons. If tumours are not caught early, they are often not detected until the cancer has metastasized. For early-stage tumours, the main treatment is surgery. Part or all of the kidney is removed, depending on the extent of the tumour. The nearby adrenal gland and lymph nodes may also be removed. Follow-up involves observing the kidneys for recurrence or spread. Clinical trials of chemotherapy, hormonal therapy and immunotherapy with interleukin-2 or interferon have all shown no difference in recurrence of tumours. Using prediction tools called nomogram tables, clinicians can assess the risk of recurrence. The table can include criteria such as the tumour's stage at the time of surgery, the patient's status (extent of symptoms or physical-activity level, for example), the tumour's grade (based on the Fuhrman grading system) and the presence of tumour necrosis. Tumours are considered to be high risk if, according to the criteria, the chance of recurrence is 40% or more. In a study earlier this year, Haas investigated the effectiveness of the antiangiogenesis drugs sunitinib and sorafenib for people with early-stage RCC who are at high risk of recurrence2. Because these drugs halted the progression of advanced cancer, the hope was that they would also prevent it from reoccurring. But that was not the case. “I was very surprised to see that in our hazard ratio, the curves were virtually the same as placebo,” Haas says. The study was stopped earlier than planned. The time to recurrence in the people who were treated with the drugs after the initial tumour was surgically removed was not significantly different to the placebo group. The question is why? Haas thinks that the answer will help researchers to better understand how RCC spreads. The targeted therapy may not have worked for early-stage RCC because, compared with large, highly vascularized metastatic tumours, the 'micrometastases' that establish new tumours when the disease reoccurs may not yet have their own blood supply, Haas explains. The drugs also caused more-severe side effects in early-stage patients than had been seen in patients with advanced cancer. These were mainly hypertension, hand–foot syndrome (calluses on hands and feet that can become raised and tender), rashes and fatigue. It is not clear why there is a higher rate of serious side effects in people with early-stage cancer, Haas says. Although the people in her study may have been healthier than later-stage patients and so have simply noticed and reported more side effects, Haas thinks that the drugs may cause worse side effects when there are no tumours. “These drugs have no tumour to hit, so they may have more 'off-target' effects,” she says. “They're hitting normal organs and making people feel worse.” Escudier says that trials are underway to investigate other VEGFR inhibitors in early-stage RCC, but he is not hopeful. “It is very likely that all of these trials are going to be negative,” he says. These drugs have also failed in other types of cancer such as breast and colorectal cancer, Escudier says. The negative results of Haas' study were “not a surprise”, he says. But there is good news. Antiangiogenesis drugs have changed the standard of care for advanced RCC, increasing lifespan with a reasonable quality of life for patients. Following a shift, initially from chemotherapy to immunotherapy and then towards antiangiogenics, the recommended protocols for which drugs to use in which sequence also changed, as new drugs moved from lab to bedside. Up to four lines of defence against RCC are needed because, in most cases, tumours eventually develop resistance to drugs that target a particular pathway. The strategy is to switch drugs — and often pathways — until the cancer eludes the therapy. Protocols can vary, but first-line treatment will involve either an immunotherapy, a VEGFR inhibitor or an mTOR inhibitor. Once resistance develops and cancer progresses, patients are switched to another therapy — either a different VEGFR or mTOR inhibitor or the checkpoint inhibitor nivolumab. But Motzer has achieved promising results by combining drugs to target three pathways at once3. He used lenvatinib, which targets both VEGFRs and fibroblast growth factor receptor (also thought to be involved in angiogenesis in RCC), combined with everolimus, which targets mTOR. The combination led to improved survival — both before the cancer progressed and overall — than everolimus alone. Although Motzer had hoped for an improved result, he was surprised at the magnitude of the improvement: the drug combination prevented cancer from progressing for a median of 14.6 months. The phase II trial led to FDA approval of lenvatinib with everolimus for advanced RCC. Motzer is now planning a randomized controlled trial that compares lenvatinib in combinations with two other drugs, with sunitinib as a control. Motzer, along with Escudier, also found that cabozantinib led to longer survival than everolimus4. “We do not know for certain why the results were so good,” says Motzer. In addition to inhibiting VEGFRs, cabozantinib inhibits two other tyrosine kinases, MET and AXL, which are found at high levels in people with clear-cell RCC and are associated with a poor prognosis. The interaction with these proteins may account for the results, says Motzer. The new therapies make the protocols for treatment a moving target. Escudier says that the priority for research now is to determine how to select the best therapy for the patient. “We really need to know how to use the drugs we have.” For example, if one drug works for about 30% of patients, how do you identify the 30% that should be given the drug? Although patients are currently stratified for therapy, according to their risk of recurrence, stage of cancer and previous treatments, the promise of personalized therapy is that treatments can be aimed at a pathway specific to the individual's cancer — selecting the right drug for the right patient. Instead of bombarding RCC with drugs that target several pathways, in the future, the target will be determined first. “Probably, in the very near future we are going to treat only those patients who have an mTOR aberration in the pathway” with mTOR inhibitors, Escudier says. But to decide the best therapy, clinicians need something that they can test for to tell them which is the relevant pathway. This can include biomarkers or genomic and next-generation sequencing methods to determine the phenotype of the tumour, Escudier says. Over the next few years, results should be available from studies examining the selection of therapy based on the tumour phenotype. Personalizing therapy would not only be more effective, but would also help to avoid the accumulated adverse effects of taking several drugs at once. Researchers also need to understand how long drugs need to be given and at what dosage. “We want to give them as much as we need to — not too much — to avoid toxicity and keep the efficacy,” says Escudier. The promising outcomes of targeted therapies are changing the treatment goals for people with advanced RCC. Clinicians used to talk in terms of progression-free survival (how long until the cancer progressed) and overall survival (how long until the patient died). Now, they are daring to talk about the disappearance of the cancer. Escudier thinks that complete remission may be achievable in 20–30% of patients in the next few years, on the basis of the rates of response to the new drugs and the increasing rates of survival that have been reported. The incremental improvements in patients' survival have been double-edged, says Escudier. “You see your patients more frequently and you become friends with them, yet in the end they die.” It is frustrating to be unable to offer a cure, he says. With new treatments and improved prognosis, Escudier is looking forward to giving them better news.


News Article | February 27, 2017
Site: www.eurekalert.org

(PRINCETON, N.J., Feb. 27, 2017) - Bristol-Myers Squibb Company (NYSE:BMY) today announced that Columbia University Medical Center and Peter MacCallum Cancer Centre (Peter Mac) have joined the International Immuno-Oncology Network (II-ON), a global peer-to-peer collaboration between Bristol-Myers Squibb and academia that aims to advance Immuno-Oncology (I-O) science and translational medicine to improve patient outcomes. Launched in 2012 by Bristol-Myers Squibb, the II-ON was one of the first networks to bring academia and industry together to further the scientific understanding of I-O, and has expanded from 10 to 15 sites including more than 250 investigators working on over 150 projects across 20 tumor types. The II-ON has generated cutting-edge I-O data that have informed the development of new I-O agents, yielded publications and produced some of the earliest findings on a variety of biomarkers and target identification and validation. "Bristol-Myers Squibb has long believed the future of cancer research is dependent on investments in science and partnerships. We formed the II-ON to facilitate innovation in I-O science and drug discovery by providing a streamlined framework for peer-to-peer collaboration among global cancer research leaders," said Nils Lonberg, Head of Oncology Biology Discovery at Bristol-Myers Squibb. "The significant discoveries generated by the II-ON over the past five years have not only informed our robust early I-O pipeline, but also serve to advance the entire field. We are proud to collaborate with Columbia University Medical Center and Peter Mac, and together with the entire II-ON will continue to lead pioneering research and heighten our collective understanding of the science behind I-O." Through the II-ON, Bristol-Myers Squibb is collaborating with leading cancer research institutions around the world to generate innovative I-O science, launch biology-driven trials and seek out cutting-edge technologies with the goal of translating research findings into clinical trials and, ultimately, clinical practice. "I-O research may be transforming the way we treat cancer," said Charles G. Drake, MD, PhD, Professor of Medicine at Columbia University Medical Center and Director of Genitourinary Oncology and Associate Director for Clinical Research at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian/Columbia. "The II-ON offers a tremendous opportunity to work smarter and faster along with our colleagues to address fundamental scientific questions in I-O." "We believe the collective knowledge and research power of the II-ON will generate groundbreaking findings in I-O with the potential to improve outcomes for people affected by cancer," said Professor Joe Trapani, Executive Director Cancer Research and Head of the Cancer Immunology Program at Peter MacCallum Cancer Centre, Melbourne, Australia. Building on the success of the II-ON, Bristol-Myers Squibb has invested in several other models of scientific collaboration with academic partners across the globe, including the Global Expert Centers Initiative (GECI) and the Immuno-Oncology Integrated Community Oncology Network (IO-ICON). "We believe a one-size-fits-all research approach does not facilitate innovation," said Lonberg. "Our tailored collaborations with academic centers expand our research capabilities and accelerate our collective ability to deliver potentially life-changing results for patients." The II-ON, formed in 2012, is a global peer-to-peer collaboration between Bristol-Myers Squibb and academia advancing the science of Immuno-Oncology (I-O) through a series of preclinical, translational and biology-focused research objectives. The research in the collaboration is focused on three fundamental scientific pillars: understanding the mechanisms of resistance to immunotherapy; identifying patient populations likely to benefit from immunotherapy; and exploring novel combination therapies that may enhance anti-tumor response through complementary mechanisms of action. The II-ON facilitates the translation of scientific research findings into drug discovery and development, with the goal of introducing new treatment options into clinical practice. In addition to Bristol-Myers Squibb, the II-ON currently comprises 15 leading cancer research institutions, including: Clinica Universidad Navarra, Dana-Farber Cancer Institute, The Earle A. Chiles Research Institute (Providence Health & Services), Institut Gustave Roussy, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, Memorial Sloan Kettering Cancer Center, National Cancer Center Japan, The Netherlands Cancer Institute, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, University College London, The University of Chicago, West German Cancer Center/University Hospital Essen, and now Columbia University Medical Center and Peter MacCallum Cancer Centre. Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer. We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents - including the first combination of two I-O agents in metastatic melanoma - and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies. We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice. Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that Columbia University Medical Center and Peter MacCallum Cancer Centre (Peter Mac) have joined the International Immuno-Oncology Network (II-ON), a global peer-to-peer collaboration between Bristol-Myers Squibb and academia that aims to advance Immuno-Oncology (I-O) science and translational medicine to improve patient outcomes. Launched in 2012 by Bristol-Myers Squibb, the II-ON was one of the first networks to bring academia and industry together to further the scientific understanding of I-O, and has expanded from 10 to 15 sites including more than 250 investigators working on over 150 projects across 20 tumor types. The II-ON has generated cutting-edge I-O data that have informed the development of new I-O agents, yielded publications and produced some of the earliest findings on a variety of biomarkers and target identification and validation. “Bristol-Myers Squibb has long believed the future of cancer research is dependent on investments in science and partnerships. We formed the II-ON to facilitate innovation in I-O science and drug discovery by providing a streamlined framework for peer-to-peer collaboration among global cancer research leaders,” said Nils Lonberg, Head of Oncology Biology Discovery at Bristol-Myers Squibb. “The significant discoveries generated by the II-ON over the past five years have not only informed our robust early I-O pipeline, but also serve to advance the entire field. We are proud to collaborate with Columbia University Medical Center and Peter Mac, and together with the entire II-ON will continue to lead pioneering research and heighten our collective understanding of the science behind I-O.” Through the II-ON, Bristol-Myers Squibb is collaborating with leading cancer research institutions around the world to generate innovative I-O science, launch biology-driven trials and seek out cutting-edge technologies with the goal of translating research findings into clinical trials and, ultimately, clinical practice. “I-O research may be transforming the way we treat cancer,” said Charles G. Drake, MD, PhD, Professor of Medicine at Columbia University Medical Center and Director of Genitourinary Oncology and Associate Director for Clinical Research at the Herbert Irving Comprehensive Cancer Center at New York-Presbyterian/Columbia. “The II-ON offers a tremendous opportunity to work smarter and faster along with our colleagues to address fundamental scientific questions in I-O.” “We believe the collective knowledge and research power of the II-ON will generate groundbreaking findings in I-O with the potential to improve outcomes for people affected by cancer,” said Professor Joe Trapani, Executive Director Cancer Research and Head of the Cancer Immunology Program at Peter MacCallum Cancer Centre, Melbourne, Australia. Building on the success of the II-ON, Bristol-Myers Squibb has invested in several other models of scientific collaboration with academic partners across the globe, including the Global Expert Centers Initiative (GECI) and the Immuno-Oncology Integrated Community Oncology Network (IO-ICON). "We believe a one-size-fits-all research approach does not facilitate innovation,” said Lonberg. “Our tailored collaborations with academic centers expand our research capabilities and accelerate our collective ability to deliver potentially life-changing results for patients." The II-ON, formed in 2012, is a global peer-to-peer collaboration between Bristol-Myers Squibb and academia advancing the science of Immuno-Oncology (I-O) through a series of preclinical, translational and biology-focused research objectives. The research in the collaboration is focused on three fundamental scientific pillars: understanding the mechanisms of resistance to immunotherapy; identifying patient populations likely to benefit from immunotherapy; and exploring novel combination therapies that may enhance anti-tumor response through complementary mechanisms of action. The II-ON facilitates the translation of scientific research findings into drug discovery and development, with the goal of introducing new treatment options into clinical practice. In addition to Bristol-Myers Squibb, the II-ON currently comprises 15 leading cancer research institutions, including: Clinica Universidad Navarra, Dana-Farber Cancer Institute, The Earle A. Chiles Research Institute (Providence Health & Services), Institut Gustave Roussy, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, Memorial Sloan Kettering Cancer Center, National Cancer Center Japan, The Netherlands Cancer Institute, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, University College London, The University of Chicago, West German Cancer Center/University Hospital Essen, and now Columbia University Medical Center and Peter MacCallum Cancer Centre. Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer. We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents – including the first combination of two I-O agents in metastatic melanoma – and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies. We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice. Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


News Article | February 22, 2017
Site: www.eurekalert.org

Death rates from cancer in the European Union (EU) are falling faster in men than in women, according to the latest predictions for European cancer deaths in 2017, published in the leading cancer journal Annals of Oncology [1] today (Wednesday). Researchers in Italy, Switzerland and the USA, led by Carlo La Vecchia (MD), Professor at the Faculty of Medicine, University of Milan (Italy), predict that, compared with 2012, death rates in men will fall by just over eight percent to 132 per 100,000 of the population in 2017, while in women the decline will be around four percent to 84.5 per 100,000. A total of 761,900 men and 611,600 women are predicted to die from all cancers in 2017. [2] "Overall, fewer women than men will die from cancer, but the fact that the rate of decline is slower in women than in men essentially reflects the different trends in lung and other tobacco-related cancers between the two sexes," said Prof La Vecchia. "In fact, death rates from lung cancer in women are still rising from their 2012 levels; we predict a rise of about five percent this year to reach an overall predicted rate of 14.5 per 100,000 women in the population, whereas lung cancer death rates in men will decrease by eleven percent to 33 per 100,000." Overall, lung cancer is predicted to cause 275,700 deaths in men and women in 2017, corresponding to about 20% of deaths from all cancers. "One striking finding is that death rates from lung cancer are higher in women between the ages of 25 and 44 than in men: 1.4 compared with 1.2 per 100,000. The difference is not significant, but it reflects the similar smoking patterns in younger generations of the two sexes over recent decades and confirms that smoking is just as harmful to women as it is to men," said Prof La Vecchia. The study looked at cancer death rates in the EU 28 member states [3] as a whole and also in the six largest countries - France, Germany, Italy, Poland, Spain and the UK - for all cancers, and, individually, for stomach, intestines, pancreas, lung, prostate, breast, uterus (including cervix) and leukaemias for men and women [4]. This is the seventh consecutive year the researchers have published these predictions and they predict that death rates for all the selected cancers will decline, with the exception of pancreatic cancer and lung cancer in women. A total of 76,100 men (10.3 per 100,000) will die from pancreatic cancer and 43,800 women (5.6 per 100,000) in 2017. While the death rate in men is stable, in women it will increase by 3.5%. "There has been little progress in the detection, treatment and prevention of pancreatic cancer and it is now the fourth highest cause of cancer death in both sexes," said Prof La Vecchia. "Although tobacco is a major risk factor for pancreatic cancer, it causes only about 15-20% of pancreatic cancers in most populations, and so there must be other contributory factors. The increased prevalence of overweight, obesity and diabetes, mostly in northern Europe, may be affecting the pancreatic cancer death rates unfavourably, and national governments and policy-makers need to do more to tackle this problem." The researchers have calculated that over four million deaths from cancer have been avoided in the 30 years since 1988. Improvements in prevention, detection and treatment of cancers (such as reducing smoking and diet improvements, screening for colorectal, breast and cervical cancers, new and better targeted drugs, and improved use of surgery and radiotherapy) mean that deaths have not continued at the same rate as in 1988, and have fallen instead. "In 2017 alone, we predict that 253,915 deaths will be avoided in men and 107,780 in women due to the fall in death rates since 1988," said Prof La Vecchia. Breast cancer death rates continue to fall in women in the EU; in 2017 a predicted 91,847 women (14 per 100,000) will die from the disease, making it the second highest cancer death rate in women after lung cancer, although the actual numbers of deaths are slightly higher than for lung cancer. Colorectal cancer death rates are falling in both sexes with predicted rates of 16.1 and 9.3 per 100,000 in men and women respectively, corresponding to 97,100 deaths in men and 78,600 in women (about 13% of total cancer deaths in both sexes). Prof Carlo La Vecchia said: "The fact that we have managed to avoid over four million deaths from cancer in the past thirty years shows the effectiveness of strategies to prevent cancer and to detect and treat it better when it arises. Apart from continuing to control tobacco use, policy-makers should build on these past achievements by measures such as optimising colorectal cancer screening and the management of breast cancer, leukaemias and other cancers amenable to treatment. This needs to be done across the whole of Europe as there is still too much variation in death rates between countries, particularly between eastern and western Europe." Co-author, Fabio Levi (MD), Emeritus Professor at the Faculty of Biology and Medicine, University of Lausanne, (Switzerland), stressed that: "The predicted persistent rise of death rates from female lung and pancreatic cancer confirm the need for effective tobacco control in European women in order to achieve, as in males, a levelling off and subsequent fall in female tobacco-related cancer rates." Editor-in-chief of Annals of Oncology, Professor Jean-Charles Soria, from the Institut Gustave Roussy (Villejuif, Paris), said: "Despite the encouraging trend of decreasing death rates in Europe in both men and to a lesser extent women, a total of 761,900 men and 611,600 women are predicted to die from all cancers in 2017 in Europe. This still represents over 1.3 million deaths from cancer in Europe, thus reflecting the amplitude and brutality of this disease." [1] "European cancer mortality predictions for the year 2017: with focus on lung cancer", by M. Malvezzi, G. Carioli, P. Bertuccio, P. Boffetta, F. Levi, C. La Vecchia and E. Negri. Annals of Oncology. doi:10.1093/annonc/mdx033 [2] Age-standardised rates per 100,000 of the population reflect the annual probability of dying. [3] The EU now has 28 member states, with Croatia joining in 2013. [4] The paper contains individual tables of cancer death rates for each of the six countries.


LONDON--(BUSINESS WIRE)--Hutchison China MediTech Limited (“Chi-Med”) (AIM/Nasdaq: HCM) and AstraZeneca PLC (“AstraZeneca”) will present data from the ongoing Phase II clinical trial of savolitinib in patients with papillary renal cell carcinoma (“PRCC”) at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology (“ASCO-GU”), to be held in Orlando, Florida from February 16 to 18, 2017. Savolitinib, a highly selective inhibitor of c-Met receptor tyrosine kinase, has shown early clinical benefit in multiple Phase I and II studies in a number of cancers. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with first-generation c-Met inhibitors, including renal toxicity. PRCC, the second most common histologic subtype of renal cell carcinoma (“RCC”), is associated with alterations in the c-Met gene (e.g. mutations, amplifications, and/or chromosomal changes). Therapies that are currently available for RCC patients have demonstrated only modest benefit in PRCC and there are no therapies specifically approved for the treatment of c-Met-driven PRCC. National Comprehensive Cancer Network guidelines recommend enrolling patients in clinical trials for first-line systemic therapy. “There is a clear unmet medical need in PRCC,” said Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “The dataset from this Phase II study is compelling, with a very clear efficacy signal in MET-driven patients and an encouraging long duration of response, while remaining very well tolerated.” He added, “These results support the initiation of the pivotal Phase III trial in a selected population of MET-driven PRCC. This innovative patient selection approach would be the first ever molecularly selected trial in renal cell carcinoma.” “We are delighted to report this highly encouraging progression-free survival data in Met-driven papillary renal cell carcinoma, a disease with no approved treatment options,” said Christian Hogg, Chief Executive Officer of Chi-Med. “With development of the companion diagnostic assay to screen Met-driven disease now also complete we are preparing for the initiation of our global Phase III study, the first global registration trial for savolitinib.” The current Phase II trial is the largest prospective clinical study ever conducted in PRCC patients. It is a global single arm study of savolitinib in 109 patients with locally advanced or metastatic PRCC and was initiated in May 2014. It is being conducted in 22 clinical centers in the US, Canada, UK, and Spain, and completed enrollment in October 2015. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02127710. The most recent results of the study will be presented in detail as follows: Once presented, the presentation will be available at www.chi-med.com/news. Further information about ASCO-GU is available at gucasym.org. Chi-Med and AstraZeneca are currently initiating a global pivotal Phase III trial, the first pivotal study ever conducted in c-Met-driven PRCC and the first molecularly selected trial in RCC. Over the course of 2017, Chi-Med and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-Met alterations and patient outcomes, including any predictive biomarkers. A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC) 1Dana-Farber Cancer Institute, Boston, US 2Fox Chase Cancer Center, Philadelphia, US 3Sarah Cannon Research Institute, London, UK 4MD Anderson Cancer Centre, Houston, US 5Tom Baker Cancer Center, Calgary, Canada 6Barts Cancer Institute, London, UK 7AstraZeneca, Waltham, US, 8AstraZeneca, Cambridge, UK 9Institute Gustave Roussy, Paris, France 10City of Hope, Duarte, US Background: Savolitinib (HMPL-504/Volitinib, AZD6094) is a potent, selective mesenchymal epithelial transition (“MET”) inhibitor (IC of 4 nM). MET and its ligand, hepatocyte growth factor (“HGF”), are known to play an important role in the molecular events underlying oncogenesis in PRCC, a disease without a clear standard of care and marked by alterations of chromosome 7 (containing both MET and HGF genes) in a majority of patients as well as gene amplification or MET kinase domain mutations (Albiges et al 2014, Linehan et al, 2015). Methods: This study evaluates savolitinib in PRCC patients dosed at 600 mg daily until disease progression. Objective Response Rate (“ORR”) is the primary endpoint. Progression-Free Survival (“PFS”) & Duration of Response are secondary endpoints. Patient Reported Outcome (“PRO”) and Health-Related Quality of Life (“HRQoL”) questionnaires are exploratory endpoints. Eligibility includes naïve and previously treated metastatic PRCC, ECOG PS 0 or 1. Archival tumor was used to centrally confirm PRCC pathology post hoc and to determine MET status using Next Generation Sequencing (Foundation Medicine Inc, US). Results: As of 27 June 2016, 109 patients were dosed. Best response was PR n=8, SD n=43, PD n=48 & 10 patients were not evaluable for response. 44 patients are MET-driven (MET/HGF gene copy number gain or kinase domain mutations), 46 patients were MET-negative, 19 patients are status unknown. MET-driven pts included Papillary Type I & II histologies. All 8 responders were in the MET-driven group, 18% ORR in this subset. Median PFS in the MET-driven group was 6.2 months (95% CI: 4.1–7.0) vs. 1.4 months (95% CI: 1.4–2.7) in the MET-negative group (p=0.002). Overall 10/109 patients had adverse events (“AEs”) leading to discontinuation. 23/109 patients had ≥ Grade 3 toxicity related to savolitinib. The most common AEs (all grades) includes: nausea (39%), fatigue (27%), edema (18%) and abnormal liver function tests (LFTs) (17%). One death from hepatic encephalopathy was considered related to savolitinib. PRO & HRQoL data was not statistically analyzed, descriptive data support main efficacy findings. Conclusions: In the largest biomarker-profiled trial dedicated to PRCC, savolitinib was generally well tolerated with anti-tumor activity in MET-driven patients. These findings warrant further clinical investigation of savolitinib in MET-driven PRCC. About the Unmet Medical Need in c-Met-Driven PRCC Patients Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually, and the total market for kidney cancer treatments is expected to reach US$4.5 billion in 2020, according to Frost & Sullivan. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. Among these histologic variants of RCC, clear cell RCC (“ccRCC”) is the most common, accounting for 75-80% of RCC. PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. The proportion of PRCC patients whose tumors are c-Met-driven has historically been estimated at 40-70%. In the largest study to date, presented at the annual meeting of the American Association for Cancer Research 2014, analysis of 220 frozen tumor samples catalogued in the French RCC Network indicated that 55-60% of PRCC patients showed gains in Chromosome 7 (i.e. c-Met amplification). The biology and molecular characteristics of PRCC are different from those of ccRCC. This results in significantly worse prognosis and treatment outcomes for patients with PRCC when compared to patients with ccRCC. Highlighting the unmet need is the fact that, although there are several drugs approved for use in RCC (the latest being approved in April 2016), these approvals were generally on the basis of studies conducted with a preponderance of ccRCC patients. The need for different agents and more specific data tailored to the PRCC disease setting has been identified as a critical gap in the care of these patients. Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare-related consumer products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China. Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com. AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology. By harnessing the power of four scientific platforms – Immuno-Oncology, the genetic drivers of cancer and resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death. AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas – Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca. This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med’s current expectations regarding future events, including its expectations for the clinical development of savolitinib, plans to initiate clinical studies for savolitinib in PRCC, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate savolitinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of savolitinib for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med’s filings with the US Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.


News Article | February 15, 2017
Site: www.marketwired.com

London: Tuesday, February 14, 2017: Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) and AstraZeneca PLC ("AstraZeneca") will present data from the ongoing Phase II clinical trial of savolitinib in patients with papillary renal cell carcinoma ("PRCC") at the 2017 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology ("ASCO-GU"), to be held in Orlando, Florida from February 16 to 18, 2017. Savolitinib, a highly selective inhibitor of c-Met receptor tyrosine kinase, has shown early clinical benefit in multiple Phase I and II studies in a number of cancers. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with first-generation c-Met inhibitors, including renal toxicity. PRCC, the second most common histologic subtype of renal cell carcinoma ("RCC"), is associated with alterations in the c-Met gene (e.g. mutations, amplifications, and/or chromosomal changes). Therapies that are currently available for RCC patients have demonstrated only modest benefit in PRCC and there are no therapies specifically approved for the treatment of c-Met-driven PRCC. National Comprehensive Cancer Network guidelines recommend enrolling patients in clinical trials for first-line systemic therapy. "There is a clear unmet medical need in PRCC," said Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. "The dataset from this Phase II study is compelling, with a very clear efficacy signal in MET-driven patients and an encouraging long duration of response, while remaining very well tolerated." He added, "These results support the initiation of the pivotal Phase III trial in a selected population of MET-driven PRCC. This innovative patient selection approach would be the first ever molecularly selected trial in renal cell carcinoma." "We are delighted to report this highly encouraging progression-free survival data in Met-driven papillary renal cell carcinoma, a disease with no approved treatment options," said Christian Hogg, Chief Executive Officer of Chi-Med. "With development of the companion diagnostic assay to screen Met-driven disease now also complete we are preparing for the initiation of our global Phase III study, the first global registration trial for savolitinib." The current Phase II trial is the largest prospective clinical study ever conducted in PRCC patients. It is a global single arm study of savolitinib in 109 patients with locally advanced or metastatic PRCC and was initiated in May 2014. It is being conducted in 22 clinical centers in the US, Canada, UK, and Spain, and completed enrollment in October 2015. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT02127710. The most recent results of the study will be presented in detail as follows: Once presented, the presentation will be available at www.chi-med.com/news. Further information about ASCO-GU is available at gucasym.org. Chi-Med and AstraZeneca are currently initiating a global pivotal Phase III trial, the first pivotal study ever conducted in c-Met-driven PRCC and the first molecularly selected trial in RCC. Over the course of 2017, Chi-Med and AstraZeneca are also conducting a comprehensive molecular epidemiology study of approximately 300 PRCC patient samples to further understand the correlations between c-Met alterations and patient outcomes, including any predictive biomarkers. ABSTRACT A single-arm biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer (PRCC) 1Dana-Farber Cancer Institute, Boston, US 2Fox Chase Cancer Center, Philadelphia, US 3Sarah Cannon Research Institute, London, UK 4MD Anderson Cancer Centre, Houston, US 5Tom Baker Cancer Center, Calgary, Canada 6Barts Cancer Institute, London, UK 7AstraZeneca, Waltham, US, 8AstraZeneca, Cambridge, UK 9Institute Gustave Roussy, Paris, France 10City of Hope, Duarte, US Background: Savolitinib (HMPL-504/Volitinib, AZD6094) is a potent, selective mesenchymal epithelial transition ("MET") inhibitor (IC of 4 nM). MET and its ligand, hepatocyte growth factor ("HGF"), are known to play an important role in the molecular events underlying oncogenesis in PRCC, a disease without a clear standard of care and marked by alterations of chromosome 7 (containing both MET and HGF genes) in a majority of patients as well as gene amplification or MET kinase domain mutations (Albiges et al 2014, Linehan et al, 2015). Methods: This study evaluates savolitinib in PRCC patients dosed at 600 mg daily until disease progression. Objective Response Rate ("ORR") is the primary endpoint. Progression-Free Survival ("PFS") & Duration of Response are secondary endpoints. Patient Reported Outcome ("PRO") and Health-Related Quality of Life ("HRQoL") questionnaires are exploratory endpoints. Eligibility includes naïve and previously treated metastatic PRCC, ECOG PS 0 or 1. Archival tumor was used to centrally confirm PRCC pathology post hoc and to determine MET status using Next Generation Sequencing (Foundation Medicine Inc, US). Results: As of 27 June 2016, 109 patients were dosed. Best response was PR n=8, SD n=43, PD n=48 & 10 patients were not evaluable for response. 44 patients are MET-driven (MET/HGF gene copy number gain or kinase domain mutations), 46 patients were MET-negative, 19 patients are status unknown. MET-driven pts included Papillary Type I & II histologies. All 8 responders were in the MET-driven group, 18% ORR in this subset. Median PFS in the MET-driven group was 6.2 months (95% CI: 4.1-7.0) vs. 1.4 months (95% CI: 1.4-2.7) in the MET-negative group (p=0.002). Overall 10/109 patients had adverse events ("AEs") leading to discontinuation. 23/109 patients had ≥ Grade 3 toxicity related to savolitinib. The most common AEs (all grades) includes: nausea (39%), fatigue (27%), edema (18%) and abnormal liver function tests (LFTs) (17%). One death from hepatic encephalopathy was considered related to savolitinib. PRO & HRQoL data was not statistically analyzed, descriptive data support main efficacy findings. Conclusions: In the largest biomarker-profiled trial dedicated to PRCC, savolitinib was generally well tolerated with anti-tumor activity in MET-driven patients. These findings warrant further clinical investigation of savolitinib in MET-driven PRCC. About the Unmet Medical Need in c-Met-Driven PRCC Patients Worldwide, about 366,000 new patients are diagnosed with kidney cancer annually, and the total market for kidney cancer treatments is expected to reach US$4.5 billion in 2020, according to Frost & Sullivan. RCC accounts for approximately 80-85% of kidney cancer and has several histological sub-types with different genetic and biochemical characteristics. Among these histologic variants of RCC, clear cell RCC ("ccRCC") is the most common, accounting for 75-80% of RCC. PRCC is the most common of the non-clear cell renal carcinomas accounting for 10-15% of RCC. The proportion of PRCC patients whose tumors are c-Met-driven has historically been estimated at 40-70%. In the largest study to date, presented at the annual meeting of the American Association for Cancer Research 2014, analysis of 220 frozen tumor samples catalogued in the French RCC Network indicated that 55-60% of PRCC patients showed gains in Chromosome 7 (i.e. c-Met amplification). The biology and molecular characteristics of PRCC are different from those of ccRCC. This results in significantly worse prognosis and treatment outcomes for patients with PRCC when compared to patients with ccRCC. Highlighting the unmet need is the fact that, although there are several drugs approved for use in RCC (the latest being approved in April 2016), these approvals were generally on the basis of studies conducted with a preponderance of ccRCC patients. The need for different agents and more specific data tailored to the PRCC disease setting has been identified as a critical gap in the care of these patients. About Chi-Med Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare-related consumer products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China. Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com. About AstraZeneca in Oncology AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca's six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in hematology. By harnessing the power of four scientific platforms - Immuno-Oncology, the genetic drivers of cancer and resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med's current expectations regarding future events, including its expectations for the clinical development of savolitinib, plans to initiate clinical studies for savolitinib in PRCC, its expectations as to whether such studies would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates, timing and availability of subjects meeting a study's inclusion and exclusion criteria, changes to clinical protocols or regulatory requirements, unexpected adverse events or safety issues, the ability of drug candidate savolitinib to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions, to gain commercial acceptance after obtaining regulatory approval, the potential market of savolitinib for a targeted indication and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med's filings with the US Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.


The joint venture made up of VINCI Construction, lead company, associated with Spie batignolles, wins a major contract on Line 15 South of the future Grand Paris Express transport network The joint venture made up of VINCI Construction, associated with Spie batignolles has won a major Grand Paris Express contract. Société du Grand Paris selected the bid submitted by this joint venture to build the T3C section of Line 15 South between the Fort d'Issy-Vanves-Clamart and Villejuif Louis Aragon stations. The €926 million pre-tax price covers construction of a tunnel with a length of more than 8 kilometres by means of two 10 metre diameter earth pressure balanced tunnel boring machines. It also includes construction of five new stations (Châtillon Montrouge, Bagneux, Arcueil-Cachan, Villejuif Institut Gustave Roussy and Villejuif Louis Aragon) and eight shafts. The project will take 70 months to complete. A large project in an urban environment The T3C section is an outsized project calling for substantial logistics. It will involve two 10 metres diameter earth pressure balanced tunnel boring machines operating simultaneously, removal of 3.2 million tonnes of spoil and placing of more than 470,000 m3 of concrete. The Villejuif Gustave-Roussy station, whose architecture and dimensions (65 metres diameter, 42 metres depth) epitomize the section, will connect Line 15 South and Line 14 South. Innovative, ambitious social measures At peak activity, the project will include nearly 900 people. Extensive steps will be taken to train and induct the long-term unemployed. Support for this work integration programme will be provided by the ViE structure (VINCI insertion Emploi), which VINCI set up in 2011 to help Group subsidiaries carry out such measures. Lastly, an endowment fund, "Chantiers et Territoires Solidaires", has been created to support public interest projects in the vicinity of the worksites. Spie batignolles is strongly committed to the integration of members of underprivileged communities, notably through the Fondation Spie Batignolles. On this occasion, VINCI Chairman and Chief Executive Officer Xavier Huillard said: "We are very proud to have won this major contract with our partner. The Grand Paris Express project is strategically important for the future and the economic development of the Greater Paris area. It will create jobs, open up regions and release energies. The Group will bring its expertise to this ambitious undertaking over the next 20 years. The project is a huge technical and also human challenge." "The Spie Batignolles Group, which has already won a number of Grand Paris contracts, once again demonstrates the quality of its teams and expertise in taking on major infrastructure projects," says Jean-Charles Robin, Chairman of the Spie Batignolles Executive Board. "The Group's wide range of business activities and ability to bring its entities together to work in synergy enable Spie Batignolles to take on projects requiring project coordination and state-of-the-art technical expertise." VINCI is a global player in concessions and construction, employing more than 183,000 people in some 100 countries. We design, finance, build and operate infrastructure and facilities that help improve daily life and mobility for all. Because we believe in all-round performance, above and beyond economic and financial results, we are committed to operating in an environmentally and socially responsible manner. And because our projects are in the public interest, we consider that reaching out to all our stakeholders and engaging in dialogue with them is essential in the conduct of our business activities. VINCI's goal is to create long-term value for its customers, shareholders, employees, and partners and for society at large. About Spie batignolles Spie batignolles, a large French construction and services group, is a major player in building and civil engineering with 6,500 employees. It operates in six main areas of expertise: construction; civil engineering and foundations; energy; public works; property; and concessions. The Group manages large construction projects and also delivers local repair and maintenance works through its nationwide network of dedicated locations. Spie batignolles leads its markets in terms of customer relationships and delivers a one-of-a-kind array of construction services. Spie batignolles has all the resources needed to manage its own growth as a completely independent entity: since September 2003, majority control of the Group has rested with its senior management team together with Ardian and Salvepar.

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