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CULVER CITY, Calif.--(BUSINESS WIRE)--NantKwest Inc. (Nasdaq:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, announced today the appointment of Leonard S. Sender, MD, as senior vice president of Medical Affairs for Pediatric, Adolescent and Young Adult Oncology. “With pediatric cancer as a leading cause of death for children in the United States, we knew that it was imperative to have someone on our team that has knowledge and expertise in identifying, diagnosing and treating patients within this demographic,” said Dr. Patrick Soon-Shiong, chairman and CEO of NantKwest. “Having Dr. Sender as part of the Cancer Breakthroughs 2020 program has proven to be invaluable as we target this deadly disease in young patients. We are excited to bring Dr. Sender on board and are confident that he will be a strong asset to our team as we continue our journey in winning the war on cancer.” Dr. Sender currently serves as the Medical Director of the Hyundai Cancer Institute at CHOC Children's Hospital as well as the Executive Director of the Pediatric, Adolescent and Young Adult Cancer Breakthroughs 2020 Program for the Chan Soon-Shiong Institute for Medicine. Prior to joining NantKwest, he was the Medical Director of Clinical Oncology at the University of California’s NCI designated Chao Family Comprehensive Cancer Center. “Since the launch of Cancer Breakthroughs 2020, I have been working with Dr. Soon-Shiong and his team on this journey to combatting cancer,” said Dr. Sender. “Childhood cancer is unique and as we continue to focus on personalized medicine, we need to think about ways we can transform the way we treat pediatrics, adolescents and young adolescents to ensure they have the best chance of survival. I am thrilled to be a part of the NantKwest team and look forward to working with my peers to research and develop effective ways to treat our young patients who have been faced with cancer.” In over 20 years of experience treating pediatric, adolescent and young adult cancer patients and survivors, Dr. Sender has seen and experienced how the field of oncology has transformed, and how concerted efforts are now made to address patients’ ancillary needs, including fertility preservation, management of acute and chronic treatment effects, and to be sensitive to the psychosocial impacts of a cancer diagnosis on those just beginning their most productive years. Dr. Sender's research interests are comprehensive and multidisciplinary, extending from epidemiological components (incidence, prevalence), to biological factors (genomic or cellular differences), to the psychosocial impact of cancer, to long-term cancer survivorship. In 2011, Dr. Sender was the recipient of a $10 million Hyundai Hope on Wheels grant to study the genomic basis of pediatric and adolescent and young adult cancers to test the hypothesis that genomic knowledge can enable clinical decisions related to treatment options. In 2010, he founded two entities critical to the development of the emerging adolescent and young adult (AYA) oncology subspecialty as President of the Society for Adolescent and Young Adult Oncology (SAYAO) and Editor-in-Chief of the Journal of Adolescent and Young Adult Oncology (JAYAO). NantKwest (NASDAQ:NK) is a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. NK cells are the body’s first line of defense due to the innate ability of NK cells to rapidly identify and destroy cells under stress, such as cancer or virally-infected cells. NantKwest’s unique NK cell-based platform, with the capacity to grow active killer cells as a biological cancer therapy, has been designed to induce cell death against cancer or infected cells by three different modes of action: (1) Direct killing using activated NK cells (aNK) that release toxic granules directly into the cell through cell to cell contact, (2) Antibody-mediated killing using haNKs, which are NK cells engineered to incorporate a high affinity receptor that binds to an administered antibody, enhancing the cancer cell killing effect of that antibody, and (3) Chimeric Antigen Receptor (CAR) activated killing using taNKs, which are NK cells engineered to incorporate CARs to target tumor-specific antigens found on the surface of cancer cells. Our aNK, haNK® and taNK™ platform addresses certain limitations of T cell therapies including the reduction of risk of serious “cytokine storms” reported after T cell therapy. As an “off-the-shelf” therapy, NantKwest’s NK cells do not rely on a patient’s own often compromised immune system. In Phase 1 clinical trials in patients with late stage cancer, NantKwest’s NK cells have been successfully administered as an outpatient infusion therapy without any reported severe side effects, even at doses of 10 billion cells. By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs that include a Phase 2 trial for a rare form of melanoma and the planned initiation of a clinical trial of NK cells targeted to breast cancer, we believe NantKwest is uniquely positioned to be the premier immunotherapy company and transform medicine by delivering living drugs in a bag and bringing novel NK cell-based therapies to routine clinical care. For more information please visit http://www.nantkwest.com and follow Dr. Soon-Shiong on Twitter @DrPatSoonShiong.


Supporters and Friends of Tilly's Life Center United for an Evening of Food, Fun and Giving to Benefit Today's Youth IRVINE, CA--(Marketwired - November 17, 2016) - This past weekend, Tilly's Life Center (TLC) held its 2nd Annual "I Am Giving" Gala at the [AV] Irvine, hosted by seven-time Emmy award-winning host, Roy Firestone to benefit TLC's youth-focused programs. Attendees rocked their best black and white attire, dined and raised over $260,000 to support TLC's mission: "to inspire today's youth to reach their full potential as productive, kind, happy and responsible individuals." "We're truly thankful for the incredible turnout at our 2nd Annual 'I Am Giving' Gala and for the support of our sponsors, volunteers and friends who made this event so special," said founder of Tilly's Life Center, Tilly Levine. "It's amazing to see our community come together and support our efforts to provide all teens with effective life tools, helping them acquire the self-confidence and self-respect needed to build a positive mind and make better choices." The gala kicked-off with a white and pink carpet entrance-leading guests into a bustling cocktail party complete with hors d'oeuvres and drinks, a TLC themed photo booth and silent auction. Key attendees at this year's gala included: Global President of Vans; Doug Palladini, Co-founder of Quiksilver; Bob McKnight, Director of the Adolescent and Young Adult (AYA) Cancer Programs at CHOC Children's Hospital and at UC Irvine Medical Center's Chao Family Comprehensive Cancer Center; Dr. Leonard Sender, President of Saddleback College; Dr. Tod Burnett, President and CEO at Tillys; Ed Thomas, Co-founder of Tillys; Hezy Shaked, CCO and Founding Partner of Urban Decay; Wende Zomnir, President/Chief Executive Officer at Anaheim Arena Management, LLC; Tim Ryan, Sr. VP of Pre-Construction at Sasco; Larry Kirkenslager and the Knights of the Stars & Stripes Tournament as well other key local influencers. Following the cocktail party, guests made their way to the main event room clapping their hands to the beat of Pharrell's "Happy" song that coincided with a video montage introducing the dynamic and inspiring Roy Firestone as Master of Ceremonies -- leaving the room filled with high spirts and positive energy. Roy Firestone kept the energy up with his impersonations of Tilly Levine, Hezy Shaked, Bob McKnight, Larry Kirkenslager and AJ Sexton that had the crowd sharing laughs with one another as they dined and mingled. Tilly Levine then took the stage to thank everyone who attended this year's gala and presented American motivational author and founder of Hay House, Louise Hay with TLC's "I Am Inspiring" award. Tilly also honored Tillys Chairman Hezy Shaked with TLC's "I Am One of a Kind" award; feeling thankful and moved, Hezy donated $50,000 to TLC. Guests were given a glimpse at how TLC has changed and touched the lives of more than 1,600 teens across Southern California over the last few years with speeches from TLC's Teen Ambassadors Chantel Bermudez, Isabella Haden and Cristian Marron. Each teen took a moment to share with attendees their personal stories and battles in which TLC has helped them overcome, such as thoughts of suicide and fighting Cancer. Following the speeches, guests were inspired to donate during the live auction to benefit the lives of teens across Southern California. Live auction items included a Bugatti driving experience, a weekend trip to Napa on a private jet for four, a four-night stay with Exclusive Resorts and more. Tilly's Life Center would like to thank all the dedicated volunteers and supporters who helped make this year's gala a success. Special thanks to event sponsors and auction donors: Tillys, Layrite, Saddleback College, Vans, BioLargo, Winston's Crown Jewelers, Latasi, Wells Fargo, SDI, Dickies, Trinitas Cellars, O'Gara Coach, LabelTex, Union Bank, Ultimate Events Inc., Trader Joe's, Winefolded and many more. For more information on Tilly's Life Center, please visit www.tillyslifecenter.org and stay connected by following @tillyslifecenter and searching these hashtags #TillysLifeCenter #TLC. TLC aims to empower teens to overcome their own adversity and crisis through positive thinking. Through tested methodologies from globally-respected thought leaders, TLC teaches effective life tools that enable teens the confidence and self-esteem they need to take responsibility for themselves -- ultimately giving them the power to make positive changes in their own lives. To find out more, please visit www.tillyslifecenter.org. Image Available: http://www.marketwire.com/library/MwGo/2016/11/17/11G122531/Images/IMG_1601-d873f48270c482998b94a3ef4320ddf0.jpg Image Available: http://www.marketwire.com/library/MwGo/2016/11/17/11G122531/Images/image2-d81fd439f95c89c0af5974c1295a1c87.jpg Image Available: http://www.marketwire.com/library/MwGo/2016/11/17/11G122531/Images/image3-dde2a461d6bcb08880cde094cc9c7650.jpg Image Available: http://www.marketwire.com/library/MwGo/2016/11/17/11G122531/Images/image4-601e285c23a6b8c5adfc4ef4f274c5f3.jpg


BEERSE, Belgien--(BUSINESS WIRE)--Janssen-Cilag International NV gab heute die bislang längsten Follow-up-Ergebnisse zur Imbruvica®▼ (Ibrutinib)-Therapie bei Patienten mit chronisch lymphatischer Leukämie (CLL) bekannt, die ein hohes und dauerhaftes Ansprechen während des Nachbeobachtungszeitraums von fünf Jahren zeigen.1 Diese aktualisierten Phase-1b/2-Studiendaten ergaben eine Gesamtansprechrate (Overall Response Rate, ORR) von 89 Prozent,2 darunter auch Patienten mit genetischen Mutationen, die mit schlechten Behandlungsergebnissen einhergehen. Eine komplette Remission (CR) wurde bei 29 Prozent der Patienten in der Erstlinientherapie beobachtet.2 Das progressionsfreie Überleben (Progression-free Survival, PFS) verbesserte sich bei frühzeitiger Einleitung der Therapie bei nicht vorbehandelten (therapie-naiven, TN) Patienten und Patienten mit rezidivierter/refraktärer (r/r) Erkrankung.2 Diese Daten (Abstract Nr. 2331) wurden am Samstag, dem 3. Dezember in einem Vortrag2 auf der 58. Jahrestagung und Ausstellung der American Society of Hematology (ASH) in San Diego, Kalifornien, vorgestellt. Weitere Follow-up-Ergebnisse der Phase-3-Studie RESONATE-2 zur Ibrutinib-Therapie über 29 Monate wurden auch am Samstag vorgestellt (Abstract Nr. 2343). Ibrutinib, ein erster Vertreter der neuen Arzneimittelklasse der Bruton-Tyrosinkinase (BTK)-Hemmer, wurde gemeinsam mit Cilag GmbH International (einer Tochtergesellschaft von Janssen) und Pharmacyclics/AbbVie entwickelt. Janssen-Partner vermarkten Ibrutinib in der EMEA-Region (Europa, Nahost und Afrika) sowie in der übrigen Welt mit Ausnahme der USA, wo es von beiden Unternehmen gemeinsam vermarket wird. „Diese Langzeitergebnisse zeigen, dass Ibrutinib Patienten helfen kann, ihre chronisch lymphatische Leukämie über längere Zeit in kompletter oder partieller Remission zu halten – und das über einen Zeitraum von fünf Jahren und ohne Chemotherapie“, kommentierte Susan O’Brien, M.D., Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center an der UC Irvine Health, Medical Director, Sue and Ralph Stern Center for Clinical Trials & Research, und eine Prüferin und Referentin der Studien PCYC-1102 und PCYC-1103.* „Weiterhin zeigen diese Ergebnisse, dass die Zeit ohne Krankheitsprogression bei Patienten länger ist, wenn die Therapie mit Ibrutinib möglichst früh im Krankheitsverlauf eingeleitet wird.” „Immer mehr Daten, die den Patientennutzen von Ibrutinib überzeugend belegen, werden verfügbar und die vorliegenden Langzeitergebnisse bei CLL geben eine wichtige Bestätigung der anhaltenden Wirkung, die mit Ibrutinib im Behandlungsverlauf erreicht werden“, so Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. „Wir freuen uns sehr, mit diesen klinisch bedeutsamen Verbesserungen die Therapielandschaft und das, was die Diagnose CCL für Patienten bedeutet, zu verändern.” Die Phase 1b/2-Studie PCYC-1102 untersuchte die Sicherheit und Wirksamkeit der Monotherapie mit Ibrutinib bei 132 Patienten mit CLL: 31 Patienten waren nicht vorbehandelt (TN): 101 Patienten waren r/r.2 Die Patienten erhielten entweder 420 mg oder 840 mg einmal täglich bis zur Krankheitsprogression oder unakzeptabler Toxizität.2 In der Gruppe der r/r Patienten hatten 34 Prozent eine Deletion del17p, 35 Prozent del11q, 47 Prozent del13q und 78 Prozent eine nicht mutierte IGHV.2 Der primäre Endpunkt war die ORR mit den sekundären Endpunkten DOR und PFS zusätzlich zur Sicherheit. Bei PCYC-1103 handelt es sich um eine Langzeit-Verlängerungsstudie. Die primären Ergebnisse dieser Studie wurden im The New England Journal of Medicine im Juni 20135 veröffentlicht und waren Grundlage der anfänglichen Zulassung von Ibrutinib in den USA für die Indikation CLL, die im Februar 2014 über den Breakthrough Therapy Designation-Antragsweg erging.6 RESONATE-2 ist eine fortgesetzte, von Pharmacyclics gesponserte, randomisierte, multizentrische, offene Phase-3-Studie, in die 269 nicht vorbehandelte Patienten mit CLL im Alter von 65 oder mehr Jahren in der EU, den USA und weiteren Regionen aufgenommen wurden. Die Patienten erhielten randomisiert entweder Ibrutinib 420 mg oral einmal täglich bis zur Krankheitsprogression oder inakzeptabler Toxizität oder Chlorambucil an den Tagen 1 und 15 eines jeden 28-tägigen Zyklus über bis zu 12 Zyklen. Die Anfangsdosis von Chlorambucil lag im 1. Zyklus bei 0,5 mg/kg und wurde je nach Verträglichkeit im 2. Zyklus in Schritten von 0,1 mg/kg auf maximal 0,8 mg/kg erhöht. Die Studie erreichte ihren primären Endpunkt und zeigte eine Verbesserung des progressionsfreien Überlebens (PFS), das von einem unabhängigen Gutachterkomitee (Independent Review Committee, IRC) beurteilt wurde. Die ersten Ergebnisse der RESONATE-2-Studie wurden im Rahmen einer Vortragsreihe auf der Tagung der American Society of Hematology (ASH) im Dezember 20158 vorgestellt und gleichzeitig im The New England Journal of Medicine veröffentlicht.7 1. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Vortrag auf der 58. Jahrestagung und Ausstellung der American Society of Hematology, San Diego, USA, 3.-6. Dezember 2016: Abstract Nr. 233. Referiert am 3. Dezember 2016. Verfügbar unter: https://ash.confex.com/ash/2016/webprogram/Paper89757.html. Zuletzt abgerufen im November 2016. 2. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Vortrag auf der 58. Jahrestagung und Ausstellung der American Society of Hematology, San Diego, USA, 3.-6. Dezember 2016. Referiert am 3. Dezember 2016. 3. Barr P, Robak T, Owen C, et al. Updated Efficacy and Safety from the Phase 3 Resonate-2 Study: Ibrutinib As First-Line Treatment Option in Patients 65 Years and Older with Chronic Lymphocytic Leukemia. Vortrag auf der 58. Jahrestagung und Ausstellung der American Society of Hematology, San Diego, USA, 3.-6. Dezember 2016: Abstract Nr. 234. Verfügbar unter: https://ash.confex.com/ash/2016/webprogram/Paper89615.html. Zuletzt abgerufen im November 2016. 5. Byrd J, Furman R, Coutre S, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42. 6. Johnson & Johnson. IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One Prior Therapy. Pressemitteilung, 12. Februar 2014. Verfügbar unter: http://www.investor.jnj.com/releasedetail.cfm?releaseid=825570. Zuletzt abgerufen im November 2016. 7. Burger J, Tedeschi A, Barr P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015:373:2435-37. 8. Janssen. Ibrutinib (IMBRUVICA®) Significantly Improved Progression-Free and Overall Survival Versus Chlorambucil in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia. Pressemitteilung, 6. Dezember 2015. Verfügbar unter: http://www.janssen.com/ibrutinib-imbruvica-significantly-improved-progression-free-and-overall-survival-versus-chlorambucil. Zuletzt abgerufen im November 2016. 9. O’Brien S, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58.


BEERSE, Belgium--(BUSINESS WIRE)--Janssen-Cilag International NV today announced the longest follow-up results to date of patients treated with Imbruvica®▼ (ibrutinib) for chronic lymphocytic leukaemia (CLL), showing high and lasting responses through five years.1 These updated Phase 1b/2 data demonstrated an overall response rate (ORR) of 89%,2 including patients with genetic mutations associated with poor outcomes. A complete response (CR) was observed in 29% of patients treated in the first-line setting.2 Progression-free survival (PFS) was improved with earlier initiation of therapy across treatment-naïve (TN) and relapsed/refractory (r/r) patients.2 These data (abstract #2331) were presented on Saturday 3 December in an oral presentation2 at the 58th Annual American Society of Hematology (ASH) Meeting and Exposition in San Diego, CA. Additional follow-up data in patients with CLL treated with ibrutinib through 29 months from the Phase 3 RESONATE-2 trial were also presented on Saturday (abstract #2343). Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is co-developed by Cilag GmbH International (an affiliate of Janssen) and Pharmacyclics/AbbVie. Janssen affiliates market ibrutinib in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where both companies co-market it. “These longer-term results demonstrate that ibrutinib can help patients keep chronic lymphocytic leukaemia in a complete or partial remission for an extended period of time, through five years, without chemotherapy,” said Susan O’Brien, M.D., Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center at UC Irvine Health, Medical Director, Sue and Ralph Stern Center for Clinical Trials & Research, and an investigator and presenter of the PCYC-1102 and PCYC-1103 trials.* “In addition, these data indicate the time without disease progression is longer for patients when treatment with ibrutinib is started as early as possible in the course of the disease.” Abstract #233: Five-Year Experience With Single-Agent Ibrutinib In Patients With Previously Untreated And Relapsed/Refractory Chronic Lymphocytic Leukaemia1,2 In these studies (PCYC-1102 and PCYC-1103), with five years of follow-up, the ORR in patients treated with ibrutinib was 89%,2 with 14% of patients achieving complete responses (CR)2 [87% ORR with 29% CR in TN patients (n=31) and 89% ORR with 10% CR in r/r patients (n=101)].2 Median time on study was 62 months (1-67) for TN patients2 and 49 months (1-67) for r/r patients.2 Overall survival (OS) at five years was 92% for TN patients and 57% for r/r patients, with a PFS rate of 92% and 43%, respectively.2 Median OS and median duration of response (DOR) was not reached. Median PFS was not reached in TN patients and was 52 months for r/r patients.2 Findings were consistent in r/r patients with high-risk CLL, and risk factors traditionally associated with poor outcomes4 including those with deletion 11q (del11q; n=28), deletion 13q (del13q; n=13), deletion 17p (del17p; n=34) and unmutated immunoglobulin heavy-chain variable-region (IGHV; n=79).2 Median PFS was 55 months (31-NE) for those with del11q, 26 months (95% CI, 18-37) for those with del17p, 43 months (95% CI, 32-not estimable) for those with unmutated IGHV, and was not reached for those with del13q.2 Results indicated PFS and OS were higher when ibrutinib treatment was started earlier.2 Median PFS was not reached in TN patients2 and was 63 months for r/r patients who received one to two prior regimens,2 59 months for those who had three prior regimens,2 and 39 months for those who had four or more prior regimens.2 “The resounding evidence in support of ibrutinib’s benefits for patients continues to grow, and this longer-term data from five years of CLL treatment provides important reassurance of the lasting effect that can be achieved with ibrutinib over time,” said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. “We are so pleased to be altering the treatment landscape and changing what a diagnosis means for CLL patients, with these clinically significant improvements.” No new safety signals emerged in the study.2 The onset of most grade three or higher treatment-emergent adverse events (TEAEs) among all patients was highest in the first year and decreased over time. The most frequent adverse events (AEs) were hypertension (26%), pneumonia (22%), neutropenia (17%) and atrial fibrillation (9%).2 The Phase 1b/2 PCYC-1102 trial evaluated safety and efficacy of single-agent ibrutinib in 132 patients with CLL: 31 patients were TN: 101 were r/r.2 Patients received either 420 mg or 840 mg once daily until disease progression or unacceptable toxicity.2 Among r/r patients, 34% had del17p, 35% del11q, 47% had del13q and 78% unmutated IGHV.2 Primary endpoint was ORR, with secondary endpoints of DOR and PFS in addition to safety. PCYC-1103 is the long-term extension study. Primary results from this trial were published in The New England Journal of Medicine in June 20135 and were the basis for the initial approval of ibrutinib in the US in CLL in February 2014 via the Breakthrough Therapy Designation pathway.6 Abstract #234: Updated Efficacy and Safety From The Phase 3 RESONATE-2 Study: Ibrutinib as First-Line Treatment Option in Patients 65 Years and Older With Chronic Lymphocytic Leukaemia3 Updated findings from the pivotal Phase 3 RESONATE-2 trial (PCYC-1115) demonstrated that at a median of 29 months of follow-up, ibrutinib continued to have substantial efficacy as first-line therapy in CLL. The study found ibrutinib reduced the risk of progression or death by 88% compared with commonly used chemotherapy agent chlorambucil. At 24 months, PFS was 89% for patients taking ibrutinib and 34% for chlorambucil [HR, 0.121; 95% CI 0.074-0.198; p<0.0001). Investigator-assessed ORR with this longer follow up was 92% with ibrutinib and 36% with chlorambucil; in the ibrutinib arm, CR or CR with incomplete bone marrow recovery (Cri) improved from 15% at 24 months to 18% with longer follow-up of 29 months. Safety findings were in line with the primary analysis of the study and found that most Grade 3 or higher AEs decreased over time. Most AEs that led to discontinuation occurred in the first year of treatment. The most frequent (≥5%) Grade ≥ 3 AEs were neutropenia (12%), pneumonia (7%), anemia (7%) and hypertension (5%). RESONATE-2 is a continuing Pharmacyclics-sponsored, randomised multi-centre, open-label, Phase 3 study which enrolled 269 treatment-naïve patients with CLL aged 65 years or older in the EU, U.S. and other regions. Patients were randomised to receive ibrutinib 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The study met its primary endpoint, demonstrating improved PFS, as assessed by an independent review committee (IRC). Initial RESONATE-2 results were presented in an oral session at the American Society of Hematology (ASH) meeting in December 20158 and simultaneously published in The New England Journal of Medicine.7 Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells.9 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.10 Ibrutinib is currently approved in Europe for the following uses:11 Please see the ibrutinib summary of product characteristics for further information.11 CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years, according to the stage of disease.12 The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options each time. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments. At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us on www.twitter.com/janssenEMEA for our latest news. Cilag GmbH International; Janssen Biotech, Inc.; and Janssen-Cilag International NV are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges inherent in product research and development, including the uncertainty of clinical success and obtaining regulatory approvals; uncertainty of commercial success for new products or new indications; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. *Disclaimer: Dr. O’Brien served as an investigator of this Pharmacyclics-sponsored clinical study. Dr. O’Brien does not have a financial interest in the company. 1. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016: Abstract #233. Presented on 3 December 2016. Available at: https://ash.confex.com/ash/2016/webprogram/Paper89757.html. Last accessed November 2016. 2. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016. Presented on 3 December 2016. 3. Barr P, Robak T, Owen C, et al. Updated Efficacy and Safety from the Phase 3 Resonate-2 Study: Ibrutinib As First-Line Treatment Option in Patients 65 Years and Older with Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016: Abstract #234. Available at: https://ash.confex.com/ash/2016/webprogram/Paper89615.html. Last accessed November 2016. 5. Byrd J, Furman R, Coutre S, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42. 6. Johnson & Johnson. IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One Prior Therapy. Press release, 12 February, 2014. Available at: http://www.investor.jnj.com/releasedetail.cfm?releaseid=825570. Last accessed November 2016. 7. Burger J, Tedeschi A, Barr P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015:373:2435-37. 8. Janssen. Ibrutinib (IMBRUVICA®) Significantly Improved Progression-Free and Overall Survival Versus Chlorambucil in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia. Press release, 6 December 2015. Available at: http://www.janssen.com/ibrutinib-imbruvica-significantly-improved-progression-free-and-overall-survival-versus-chlorambucil. Last accessed November 2016. 9. O’Brien S, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58. 10. European Medicines Agency. IMBRUVICA (ibrutinib). Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003791/human_med_001801.jsp&mid=WC0b01ac058001d124. Last accessed November 2016. 11. Imbruvica Summary of Product Characteristics, October 2016. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003791/WC500177775.pdf. Last accessed November 2016.


BEERSE, Belgio--(BUSINESS WIRE)--Janssen-Cilag International NV ha annunciato in data odierna i risultati di follow-up più estesi ad oggi relativi a pazienti affetti da leucemia linfatica cronica (LLC) trattati con Imbruvica®▼ (ibrutinib), dimostrando risposte elevate e durature per cinque anni.1 Questi dati aggiornati di fase 1b/2 hanno dimostrato un tasso di risposta complessiva (Overall Response Rate, ORR) dell’89%2 compresi pazienti con mutazioni genetiche associate a scarsi risultati. Una risposta completa (Complete Response, CR) è stata osservata nel 29% dei pazienti trattati nell’ambito della prima linea.2 La sopravvivenza libera da progressione (Progression-Free Survival, PFS) è migliorata avviando prima la terapia in pazienti non trattati in precedenza (Treatment Naïve, TN) e in pazienti recidivanti/refrattari (r/r).2 Questi dati (abstract #2331) sono stati illustrati sabato 3 dicembre con una presentazione orale2 nell'ambito del 58th Annual American Society of Hematology (ASH) Meeting and Exposition svoltosi a San Diego, CA. “Questi risultati a lungo termine hanno dimostrato che ibrutinib può aiutare i pazienti a mantenere la leucemia linfatica cronica in remissione completa o parziale per un periodo esteso di tempo, fino a cinque anni, senza chemioterapia”, ha spiegato Susan O’Brien, M.D., Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center presso UC Irvine Health, Medical Director, Sue and Ralph Stern Center for Clinical Trials & Research, nonché ricercatrice e presentatrice degli studi clinici PCYC-1102 e PCYC-1103.* “Questi dati indicano inoltre che il periodo libero da progressione della malattia è più esteso per i pazienti quando il trattamento con ibrutinib viene avviato prima possibile nel corso della malattia.” Abstract #233: Five-Year Experience With Single-Agent Ibrutinib In Patients With Previously Untreated And Relapsed/Refractory Chronic Lymphocytic Leukaemia (Esperienza di cinque anni con ibrutinib in monoterapia in pazienti con leucemia linfatica cronica recidivata/refrattaria non trattati in precedenza)1,2 In questi studi (PCYC-1102 e PCYC-1103), con cinque anni di follow-up, l'ORR nei pazienti trattati con ibrutinib è stato dell'89%,2 con 14% dei pazienti che ottenevano risposte complete (CR)2 [ORR dell'87% con 29% di CR in pazienti TN (n=31) e ORR dell'89% ORR con 10% di CR in pazienti r/r (n=101)].2 La durata mediana dello studio è stata di 62 mesi (1-67) per i pazienti TN2 e 49 mesi (1-67) per i pazienti r/r.2 La sopravvivenza complessiva (Overall Survival, OS) a cinque anni è stata pari al 92% per i pazienti TN e al 57% per i pazienti r/r, con un tasso PFS rispettivamente del 92% e del 43%.2 L’OS mediana e la durata mediana della risposta (Duration of Response, DOR) non sono state raggiunte. La PFS mediana non è stata raggiunta nei pazienti TN ed è stata di 52 mesi per i pazienti r/r.2 I risultati sono stati coerenti nei pazienti r/r con LLC ad alto rischio e fattori di rischio tradizionalmente associati a risultati scarsi4 compresi quelli con delezione 11q (del 11q; n=28), delezione 13q (del 13q; n=13), delezione 17p (del 17p; n=34) e regione variabile delle catene pesanti delle immunoglobuline (IGHV) immutata (n=79).2 La PFS mediana era di 55 mesi (31-NE) per i pazienti con del 11q, 26 mesi (95% CI, 18-37) per i pazienti con del 17p, 43 mesi (95% CI, 32-non calcolabile) per i pazienti con IGHV immutato, e non è stata raggiunta per i pazienti con del 13q.2 I risultati hanno indicato che PFS e OS erano maggiori quando la terapia con ibrutinib veniva avviata prima.2 La PFS mediana non è stata raggiunta nei pazienti TN2 ed è stata di 63 mesi per i pazienti r/r che avevano già ricevuto uno o 2 regimi,2 59 mesi per i pazienti che avevano già ricevuto tre regimi,2 e 39 mesi per quanti avevano già ricevuto quattro o più regimi.2 “L’evidenza definitiva a supporto dei benefici di ibrutinib per i paizenti continua a crescere, e questi dati provenienti da un periodo più esteso di cinque anni di trattamento della LLC offrono importanti rassicurazioni sull’effetto duraturo ottenibile con ibrutinib nel tempo”, ha dichiarato Jane Griffiths, presidente del gruppo Janssen per l’Europa, Medio Oriente e Africa. “Siamo così entusiasti di cambiare lo scenario terapeutico e il significato della diagnosi per i pazienti con LLC, grazie a questi miglioramenti clinicamente significativi”. Lo studio clinico di Fase 1b/2 PCYC-1102 ha valutato la sicurezza e l’efficacia della monoterapia a base di ibrutinib in 132 pazienti affetti da LLC: 31 pazienti erano TN: 101 erano r/r.2 I pazienti hanno ricevuto 420 mg o 840 mg una volta al giorno fino alla progressione della malattia o tossicità inaccettabile.2 Fra i pazienti r/r, 34% avevano del 17p, 35% del 11q, 47% avevano del 13q e 78% IGHV immutato.2 L’endpoint primario era la ORR, con endpoint secondari DOR e PFS oltre alla sicurezza. PCYC-1103 è lo studio di estensione a lungo termine. I risultati primari di questo studio clinico sono stati pubblicati in The New England Journal of Medicine nel giugno 20135 e hanno costituito la base dell’approvazione iniziale di ibrutinib per il trattamento della LLC negli Stati Uniti nel febbraio 2014 mediante la designazione di breakthrough therapy (farmaco fortemente innovativo).6 Abstract #234: Updated Efficacy and Safety From The Phase 3 RESONATE-2 Study: Ibrutinib as First-Line Treatment Option in Patients 65 Years and Older With Chronic Lymphocytic Leukaemia (Dati aggiornati di efficacia e sicurezza dallo studio clinico di Fase III RESONATE-2: ibrutinib come opzione terapeutica di prima linea in pazienti di almeno 65 anni di età affetti da leucemia linfatica cronica)3 I risultati aggiornati dello studio pivotale di fase III RESONATE-2 (PCYC-1115) hanno dimostrato che a un follow-up mediano di 29 mesi, ibrutinib ha continato ad avere notevole efficacia come terapia di prima linea nella LLC. Secondo i risultati dello studio, ibrutinib ha ridotto il rischio di progressione o morte dell’88% rispetto a clorambucile, l’agente chemioterapico comunemente impiegato. A 24 mesi, il tasso di PFS era dell'89% per i pazienti trattati con ibrutinib e del 34% per il braccio trattato con clorambucile [HR, 0,121; 95% CI 0,074-0,198; p<0,0001). L’ORR valutato dai ricercatori con questo follow-up più esteso era del 92% con ibrutinib e del 36% con clorambucile; nel braccio trattato con ibrutinib, la CR o CR con recupero incompleto del midollo osseo (Cri) migliorava dal 15% a 24 mesi al 18% con un follow-up più esteso di 29 mesi. RESONATE-2 è uno studio clinico randomizzato, in aperto, multicentrico di fase III in corso sponsorizzato da Pharmacyclics, condotto fra 269 pazienti affetti da LLC di almeno 65 anni di età, non trattati in precedenza, nell'UE, negli Stati Uniti e in altre regioni del mondo. I pazienti sono stati randomizzati per ricevere un dose orale giornaliera di ibrutinib 420 mg fino a progressione della malattia o tossicità inaccettabile, oppure clorambucile nei giorni 1 e 15 di ogni ciclo di 28 giorni, fino a un massimo di 12 cicli. La dose iniziale per clorambucile nel Ciclo 1 era di 0,5 mg/kg, incrementata sulla base della tollerabilità nel Ciclo 2 per incrementi di 0,1 mg/kg fino a un massimo di 0,8 mg/kg. Lo studio ha incontrato il suo endpoint primario, dimostrando un miglioramento della PFS, valutata da un comitato di revisione indipendente (IRC). I risultati iniziali di RESONATE-2 erano stati presentati in una sessione orale al meeting dell'American Society of Hematology (ASH) nel dicembre 20158 e pubblicati simultaneamente su The New England Journal of Medicine.7 Le società del gruppo Janssen Pharmaceutical Companies di Johnson & Johnson sono impegnate a eliminare le malattie dal mondo: trasformare la vita con nuovi e migliorati metodi per prevenire, intercettare, trattare e curare le malattie è la nostra fonte di ispirazione. Riuniamo le menti migliori e scegliamo i percorsi scientifici più promettenti. Siamo il marchio Janssen. Collaboriamo a livello internazionale per la salute di tutti, in tutto il mondo. Per ulteriori informazioni visitare il sito www.janssen.com. Per le notizie più aggiornate seguiteci su www.twitter.com/janssenEMEA. Il presente comunicato stampa contiene "dichiarazioni a carattere previsionale" secondo la definizione del Private Securities Litigation Reform Act del 1995 relativa allo sviluppo di un prodotto. Si avvisano i lettori di non fare affidamento su tali dichiarazioni a carattere previsionale, che si basano sulle aspettative correnti per eventi futuri. Nel caso in cui le ipotesi di base dovessero rivelarsi imprecise, o si dovessero concretizzare rischi noti o sconosciuti o incertezze, i risultati effettivi potrebbero presentare differenze materiali con le aspettative e le previsioni di Janssen-Cilag International NV e/o di Johnson & Johnson. Rischi e incertezze includono, ma non a titolo esaustivo: difficoltà e incertezze nello sviluppo del prodotto, compresa l'incertezza del successo clinico e dell’ottenimento delle autorizzazioni previste dalla legge; incertezza del successo commerciale di nuovi prodotti o nuove indicazioni; la concorrenza, compresi progressi tecnologici, nuovi prodotti e brevetti ottenuti dai concorrenti; difficoltà relative ai brevetti; cambiamenti nelle leggi e normative, comprese riforme globali nell'assistenza sanitaria; e la tendenza al contenimento dei costi in ambito di assistenza sanitaria. Un ulteriore elenco con la descrizione di questi rischi, incertezze e altri fattori è riportato nella relazione annuale di Johnson & Johnson sul modello Form 10-K relativa all’esercizio terminato il 3 gennaio 2016, nell’Exhibit 99 accluso, e nei documenti successivamente depositati dall’azienda presso la Securities and Exchange Commission. Copie di questi documenti sono disponibili online all’indirizzo www.sec.gov, www.jnj.com oppure possono essere richieste a Johnson & Johnson. Nessuna delle società di Janssen Pharmaceutical Companies o di Johnson & Johnson si impegna ad aggiornare tali dichiarazioni a carattere previsionale a seguito di nuove informazioni o di eventi o sviluppi futuri. 1. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Presentazione orale al 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 dicembre 2016: Abstract #233. Presentato il 3 dicembre 2016. Disponibile su: https://ash.confex.com/ash/2016/webprogram/Paper89757.html. Ultimo accesso novembre 2016. 2. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Presentazione orale al 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 dicembre 2016. Presentato il 3 dicembre 2016. 3. Barr P, Robak T, Owen C, et al. Updated Efficacy and Safety from the Phase 3 Resonate-2 Study: Ibrutinib As First-Line Treatment Option in Patients 65 Years and Older with Chronic Lymphocytic Leukemia. Presentazione orale al 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 dicembre 2016: Abstract #234. Disponibile su: https://ash.confex.com/ash/2016/webprogram/Paper89615.html. Ultimo accesso novembre 2016. 5. Byrd J, Furman R, Coutre S, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42. 6. Johnson & Johnson. IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One Prior Therapy. Comunicato stampa, 12 febbraio, 2014. Disponibile su: http://www.investor.jnj.com/releasedetail.cfm?releaseid=825570. Ultimo accesso novembre 2016. 7. Burger J, Tedeschi A, Barr P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015:373:2435-37. 8. Janssen. Ibrutinib (IMBRUVICA®) Significantly Improved Progression-Free and Overall Survival Versus Chlorambucil in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia. Comunicato stampa, 6 dicembre 2015. Disponibile su: http://www.janssen.com/ibrutinib-imbruvica-significantly-improved-progression-free-and-overall-survival-versus-chlorambucil. Ultimo accesso novembre 2016. 9. O’Brien S, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58.


Gong X.,University of California at Irvine | Schwartz P.H.,Childrens Hospital | Linskey M.E.,University of California at Irvine | Linskey M.E.,Chao Family Comprehensive Cancer Center | And 2 more authors.
Neurology | Year: 2011

Objectives: New data suggest that glioma stem-like cells (GSCs) and neural stem/progenitor cells (NSCs) may share common origins. GSCs drive tumor proliferation and appear to be resistant to classic chemotherapy, while the effects of chemotherapy on NSCs are not well studied. As the role of NSCs in learning and memory is increasingly recognized, we need to identify drugs that reduce neurotoxicity but are still effective against glial tumors. Methods: We treated 3 human NSC cultures and multiple low- and high-grade GSC cultures with the commonly used agents temozolomide (TMZ) and cisplatin (CIS), and with 2 newer, promising drugs: the proteasome inhibitor bortezomib (BTZ) and the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib (ERL). We measured cell survival, proliferation, cell death induction, and drug resistance markers. Results: TMZ decreased NSC viability, while minimally affecting GSCs. TMZ induced NSC death, which was partially compensated for by increased proliferation. CIS had similar effects. The NSC's sensitivity to TMZ and CIS correlated with low expression of the multidrug resistance gene ABCG2, but not of MGMT or MSH1/MLH2. BTZ caused an 80% decrease in GSCs, while minimally affecting NSCs. GSCs had lower proteasome levels and activity after BTZ treatment. ERL treatment also decreased GSC numbers, but not NSC viability, which correlated with low EGFR expression in NSCs compared to GSCs. Conclusions: Newer chemotherapy agents ERL and BTZ are effective against GSCs yet produce minimal effects on NSCs, while the older drugs TMZ and CIS are more toxic for NSCs than for GSCs. The identification and testing of more selective drugs is clearly warranted. © 2011 by AAN Enterprises, Inc. All rights reseved.


BEERSE, Belgique--(BUSINESS WIRE)--Janssen-Cilag International NV a annoncé les résultats du plus long suivi réalisé à ce jour pour des patients suivant un traitement à l'Imbruvica®▼ (ibrutinib) contre la leucémie lymphoïde chronique (LLC), faisant état de réponses élevées et durables sur cinq ans.1 Ces données mises à jour de Phase 1b/2 ont montré un taux de réponse globale (TRG) de 89%,2 y compris les patients avec des mutations génétiques associées à des pronostics médiocres. Une réponse complète (RC) a été observée chez 29% des patients traités en première ligne.2 La survie sans progression de la maladie (SSPM) s'est améliorée en lançant plus tôt le traitement chez les patients naïfs de traitement (NT) et les patients en rechute ou réfractaires (r/r).2 Ces données (résumé #2331) ont été présentées samedi 3 décembre lors d'une présentation orale2 prononcée à la 58e conférence et exposition annuelles de l'American Society of Hematology (ASH) à San Diego, en Californie. Les données du suivi chez les patients atteints de LLC et traités à l'ibrutinib pendant 29 mois à partir de la Phase 3 de l'essai RESONATE-2 ont également été présentées samedi (résumé #2343). L'ibrutinib, inhibiteur de premier ordre de la tyrosine kinase de Bruton (BTK), est développé conjointement par Cilag GmbH International (une filiale de Janssen) et Pharmacyclics/AbbVie. Les filiales de Janssen commercialisent l’ibrutinib dans la région EMOA (Europe, Moyen-Orient et Afrique) ainsi que dans le reste du monde, à l’exception des États-Unis, où les deux sociétés assurent une commercialisation conjointe. « Ces résultats à plus long terme démontrent que l'ibrutinib peut aider les patients atteints de leucémie lymphoïde chronique à rester dans un état de rémission complète ou partielle sur une longue période de cinq années, sans chimiothérapie », déclare Susan O’Brien, DG, directrice adjointe des Sciences cliniques, au Chao Family Comprehensive Cancer Center de l'UC Irvine Health, directrice médicale, au Sue and Ralph Stern Center for Clinical Trials & Research, et chercheur et présentatrice des essais PCYC-1102 et PCYC-1103.* « De plus, ces données indiquent que la durée sans progression de la maladie est plus longue lorsque le traitement à l'ibrutinib est démarré le plus tôt possible. » Dans ces études (PCYC-1102 et PCYC-1103), avec cinq années de suivi, le TRG chez les patients traités à l'ibrutinib était de 89%,2 avec 14% des patients atteignant une réponse complète (RC)2 [TRG de 87% avec 29% de RC chez les patients NT (n=31) et TRG de 89% avec 10% de RC chez les patients r/r (n=101)].2 La durée médiane d'étude était de 62 mois (1-67) pour les patients NT2 et de 49 mois (1-67) pour les patients r/r.2 La survie globale (SG) à cinq ans était de 92% pour les patients NT et de 57% pour les patients r/r, avec un taux respectif de SSPM de 92% et 43%.2 La SG médiane et la durée de réponse médiane n'ont pas été atteintes. La SSPM médiane n'a pas été atteinte pour les patients NT, et était de 52 mois pour les patients r/r.2 Les résultats étaient cohérents chez les patients r/r atteints de LLC à risque élevé, et les facteurs de risques ont traditionnellement été associés à des pronostics médiocres4 y compris pour ceux avec délétion 11q (del11q; n=28), délétion 13q (del13q; n=13), délétion 17p (del17p; n=34) et une région variable de chaîne lourde d'immunoglobuline non mutée (IGHV; n=79).2 La SSPM médiane était de 55 mois (31-NE) pour ceux avec del11q, 26 mois (95% CI, 18-37) pour ceux avec del17p, 43 mois (95% CI, 32-non estimable) pour ceux avec une IGHV non mutée, et n'a pas était atteinte pour ceux avec del13q.2 Les résultats ont indiqué que la SSPM et la SG étaient supérieures lorsque le traitement à l'ibrutinib démarré plus tôt.2 La SSPM médiane n'a pas été atteinte chez les patients NT2 et était de 63 mois pour les patients r/r qui avaient déjà reçu un ou deux régimes médicamenteux,2 de 59 mois pour ceux qui avaient déjà reçu trois régimes,2 et de 39 mois pour ceux qui avaient déjà reçu quatre régimes ou plus.2 « Les preuves irréfutables en faveur des avantages de l'ibrutinib pour les patients continuent d'arriver, et ces données à plus long terme, pendant cinq années de traitement anti LLC, sont une importante confirmation des effets durables qui peuvent être obtenus avec l'ibrutinib », souligne Jane Griffiths, présidente du groupe Janssen Europe, Moyen-Orient et Afrique. « Grâce à ces améliorations cliniques significatives, nous sommes heureux de modifier l'horizon thérapeutique et les diagnostics pour les patients atteints de LLC. » Aucun nouveau signal d'innocuité n'a été constaté durant l'étude.2 L'apparition d'effets indésirables en cours de traitement de niveau trois ou supérieur, pour tous les patients, était plus élevée au cours de la première année et a diminué avec le temps. Les effets indésirables les plus fréquents ont été l'hypertension (26%), la pneumonie (22%), la neutropénie (17%) et la fibrillation auriculaire (9%).2 La Phase 1b/2 de l'essai PCYC-1102 a évalué l'innocuité et l'efficacité de l'ibrutinib en monothérapie chez 132 patients atteints de LLC: 31 patients étaient NT: 101 étaient r/r.2 Les patients ont reçu 420 mg ou 840 mg une fois par jour jusqu'à progression de la maladie ou jusqu'à un niveau de toxicité inacceptable.2 Parmi les patients r/r, 34% étaient del17p, 35% del11q, 47% del13q et 78% IGHV non mutée.2 Le critère principal était le TRG, et les critères secondaires étaient la durée de réponse et la SSPM, en plus de l'innocuité. La PCYC-1103 est l'étude d'extension longue durée. Les résultats primaires de cet essai avaient été publiés dans The New England Journal of Medicine en juin 20135 et ont servi de base à l'approbation initiale de l'ibrutinib aux États-Unis pour les patients atteints de LLC en février 2014 avec l'obtention de la Breakthrough Therapy Designation.6 Résumé #234: Efficacité et innocuité mises à jour pour la Phase 3 de l'étude RESONATE-2: l'ibrutinib en tant qu'option thérapeutique de première ligne pour les patients âgés de 65 ans et plus atteints de leucémie lymphoïde chronique3 Les résultats mis à jour de l'étude pivot RESONATE-2 de Phase 3 (PCYC-1115) ont démontré qu'à une moyenne de 29 mois de suivi, l'ibrutinib continuait d'avoir une efficacité substantielle en tant que thérapie de première ligne contre la LLC. Selon l'étude, l'ibrutinib a réduit de 88% le risque de progression ou de décès en comparaison avec le chlorambucil, un agent de chimiothérapie communément utilisé. À 24 mois, la SSPM était de 89% pour les patients prenant de l'ibrutinib et de 34% pour le chlorambucil [HR, 0,121; 95% CI 0,074-0,198; p<0,0001). Le TRG évalué par les chercheurs pendant ce suivi de plus longue durée était de 92% avec l'ibrutinib et de 36% avec le chlorambucil ; avec l'ibrutinib, les RC ou RC avec rétablissement médullaire incomplet ont connu une amélioration, passant de 15% à 24 mois, à 18% avec un suivi de 29 mois. Les résultats d'innocuité étaient conformes avec l'analyse primaire de l'étude, et ont démontré que les effets indésirables de niveau 3 ou supérieur ont diminué avec le temps. La plupart des effets indésirables qui ont conduit à un abandon thérapeutique se sont produits durant la première année de traitement. Les effets indésirables de niveau ≥ 3 les plus fréquents (≥5%) étaient la neutropénie (12%), la pneumonie (7%), l'anémie (7%) et l'hypertension (5%). RESONATE-2 est une étude en cours de Phase 3, sponsorisée par Pharmacyclics, randomisée, multicentrique et ouverte, réalisée auprès de 269 patients naïfs de traitement et atteints de LLC, âgés de 65 ans et plus, dans l'UE, aux États-Unis et dans d'autres régions. Les patients ont été randomisés pour recevoir de l'ibrutinib 420 mg par voie orale, une fois par jour jusqu'à progression ou toxicité inacceptable, ou du chlorambucil les jours 1 et 15 de chaque cycle de 28 jours et jusqu'à 12 cycles. La dose de départ de chlorambucil pendant le Cycle 1 était de 0,5 mg/kg et a été augmentée en fonction de la tolérabilité pendant le Cycle 2 par paliers de 0,1 mg/kg jusqu'à un maximum de 0,8 mg/kg. L'étude a validé son critère principal en démontrant une amélioration de la SSPM, telle qu'évaluée par un comité d'évaluation indépendant. Les résultats initiaux de RESONATE-2 avaient été présentés au cours d'une session orale à la conférence de l'American Society of Hematology (ASH) en décembre 20158 et publiés simultanément dans The New England Journal of Medicine.7 La LLC est une maladie chronique ; la durée de survie globale médiane varie entre 18 mois et plus de 10 ans en fonction du stade de la maladie.12 La maladie évolue finalement chez la majorité des patients, et les patients ont à chaque fois un nombre plus réduit d’options de traitement. On prescrit souvent aux patients de multiples lignes de traitement lorsqu’ils rechutent ou deviennent résistants aux traitements. Dans les sociétés pharmaceutiques Janssen du groupe Johnson & Johnson, nous œuvrons à créer un monde sans maladie. Transformer les vies en trouvant des moyens nouveaux et meilleurs pour prévenir, intercepter, traiter et guérir les maladies est pour nous une source d'inspiration. Nous réunissons les plus brillants esprits et recherchons la science la plus prometteuse. Nous sommes Janssen. Nous collaborons dans le monde entier au service de la santé de tous. Pour en savoir plus, rendez-vous sur www.janssen.com. Suivez-nous sur www.twitter.com/janssenEMEA pour connaître toute notre actualité. Le présent communiqué de presse contient des « énoncés prospectifs » au sens de la loi Private Securities Litigation Reform Act de 1995 pour ce qui concerne le développement de produits. Il est conseillé au lecteur de ne pas placer une confiance excessive dans ces énoncés prospectifs. Ces énoncés sont fondés sur les attentes actuelles par rapport à des événements futurs. Si les suppositions sous-jacentes s’avèrent inexactes ou si des risques ou incertitudes, connus ou inconnus, se matérialisent, les résultats réels pourraient différer sensiblement des attentes et projections de Janssen-Cilag International NV et/ou de Johnson & Johnson. Les risques et incertitudes incluent, sans toutefois s’y limiter : les défis et incertitudes inhérents au développement de produits, y compris l’incertitude quant à la réussite clinique et à l’obtention des autorisations réglementaires ; l’incertitude quant au succès commercial ; la concurrence, y compris les progrès technologiques, les nouveaux produits et brevets obtenus par nos concurrents ; les difficultés ou retards dans la fabrication ; la contestation de brevets ; les préoccupations concernant l’efficacité ou l’innocuité de produits résultant de rappels de produits ou d’actions réglementaires ; les modifications des comportements et des habitudes d’achat ou les difficultés financières des acheteurs de produits et de services de soins de santé ; ainsi que les tendances envers la maîtrise des coûts des soins de santé. Une liste et une description plus exhaustives de ces risques, incertitudes et autres facteurs figurent dans le rapport annuel de Johnson & Johnson sur formulaire 10-K pour l’exercice clos au 3 janvier 2016, notamment dans la partie 99 de celui-ci, et dans les documents déposés ultérieurement par la société auprès de la Commission américaine des opérations de Bourse (la « SEC »). Des exemplaires de ces documents sont disponibles en ligne sur www.sec.gov, www.jnj.com ou sur demande auprès de Johnson & Johnson. Aucune des sociétés pharmaceutiques Janssen, ni Johnson & Johnson n’assume l’obligation de mettre à jour un quelconque énoncé prospectif suite à de nouvelles informations ou à des événements ou développements futurs. 1. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016: Abstract #233. Presented on 3 December 2016. Disponible sur: https://ash.confex.com/ash/2016/webprogram/Paper89757.html. Dernière consultation novembre 2016. 2. O’Brien S, Furman R, Coutre S, et al. Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016. Presented on 3 December 2016. 3. Barr P, Robak T, Owen C, et al. Updated Efficacy and Safety from the Phase 3 Resonate-2 Study: Ibrutinib As First-Line Treatment Option in Patients 65 Years and Older with Chronic Lymphocytic Leukemia. Oral presentation at the 58th Annual Meeting and Exposition of the American Society of Hematology, San Diego, USA, 3-6 December 2016: Abstract #234. Disponible sur: https://ash.confex.com/ash/2016/webprogram/Paper89615.html. Dernière consultation novembre 2016. 5. Byrd J, Furman R, Coutre S, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42. 6. Johnson & Johnson. IMBRUVICA™ (ibrutinib) Now Approved in the U.S. for Patients with Chronic Lymphocytic Leukemia Who Have Received At Least One Prior Therapy. Press release, 12 February, 2014. Disponible sur: http://www.investor.jnj.com/releasedetail.cfm?releaseid=825570. Dernière consultation novembre 2016. 7. Burger J, Tedeschi A, Barr P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015:373:2435-37. 8. Janssen. Ibrutinib (IMBRUVICA®) Significantly Improved Progression-Free and Overall Survival Versus Chlorambucil in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia. Press release, 6 December 2015. Disponible sur: http://www.janssen.com/ibrutinib-imbruvica-significantly-improved-progression-free-and-overall-survival-versus-chlorambucil. Dernière consultation novembre 2016. 9. O’Brien S, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58.


Monk B.J.,Chao Family Comprehensive Cancer Center | Willmott L.J.,Chao Family Comprehensive Cancer Center | Sumner D.A.,Chao Family Comprehensive Cancer Center
Gynecologic Oncology | Year: 2010

While the incidence of cervical cancer has declined significantly in the United States, it still remains a serious American health threat. When detected early, cervical cancer is generally curable. Early lesions are treated surgically, and locally advanced lesions are managed with concurrent cisplatin chemotherapy and pelvic radiation. Metastatic disease or recurrent lesions not amenable to radical local excision or regional radiation are treated with palliative chemotherapy. Current chemotherapeutic regimens are associated with significant side effects and only limited activity making the identification of active and tolerable novel targeted agents a high priority. Angiogenesis is central to cervical cancer development and progression. The dominant role of angiogenesis in cervical cancer seems to be directly related to HPV inhibition of p53 and stabilization of HIF-1 alpha, both of which increase VEGF. Bevacizumab binding and subsequent inactivation of VEGF seem to shrink cervical tumors and delay progression without appreciable toxicity, and are therefore being studied in a Gynecologic Oncology Group (GOG) phase III trial. Other intracellular tyrosine kinase inhibitors (TKIs) of angiogenesis such as pazopanib are also encouraging, especially in lieu of their oral administration. Further study of angiogenesis and its inhibition are ongoing. © 2009 Elsevier Inc. All rights reserved.


Randall L.M.,Chao Family Comprehensive Cancer Center | Monk B.J.,Chao Family Comprehensive Cancer Center
Gynecologic Oncology | Year: 2010

Objectives: The purpose of this review is to discuss the side effect profile of bevacizumab, to discuss proposed mechanisms of these toxicities, and to provide suggestions for management of adverse events. Methods: A search of MEDLINE and ASCO and SGO abstract databases of articles published between January 1970 and August 2009 addressing the toxicity of bevacizumab in solid tumors was conducted. Reporting was limited to best available evidence including any available phase III studies and ovarian cancer phase II studies. Original publications addressing underlying mechanisms of bevacizumab toxicities were included. Results: Extensive experience with bevacizumab has proven the agent to be generally well tolerated, with an adverse event profile distinct from traditional cytotoxic chemotherapy and likely peculiar to its novel mechanism of action. The most common bevacizumab-attributable adverse event, hypertension, can be medically-managed, but more serious adverse events such as bowel perforation require drug discontinuation. Conclusions: Current best evidence supports the use of bevacizumab in selected patients, and safe administration of bevacizumab requires an understanding of the management of adverse events attributable to its use. © 2010 Elsevier Inc. All rights reserved.


Ou S.-H.I.,University of California at Irvine | Ou S.-H.I.,Chao Family Comprehensive Cancer Center
Cancer | Year: 2015

The treatment of lung cancer has advanced since 2009, the end of the study period for Sacher et al's study. The use of genomic profiling for lung cancer and the use of targeted immunotherapy should be analyzed in the coming years with Sacher et al's study as a reference. © 2015 American Cancer Society.

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