Dreicer R.,Cleveland Clinic |
Bajorin D.F.,Cornell University |
Bajorin D.F.,Sloan Kettering Cancer Center |
McLeod D.G.,U.S. Army |
And 3 more authors.
Urology | Year: 2011
Until the 1980s, testosterone suppression for men with advanced prostate cancer was managed surgically, with bilateral orchiectomy, or medically, with diethylstilbestrol, a drug that was associated with a problematic side effect profile. Beginning in the mid-1980s, the U.S. Food and Drug Administration approved the first luteinizing hormone-releasing hormone agonists, which proved effective for suppressing circulating testosterone levels and led to a significant shift away from surgical castration to medical management during the past 25 years. The luteinizing hormone-releasing hormone agonists resulted in a periodic return of noncastrate testosterone levels once the receptor desensitization attenuated and the effect of androgen agonism resumed. Therefore, the introduction of an androgen receptor antagonist (gonadotropin-releasing hormone antagonist) appeared, conceptually at least, to be a preferable alternative. The first such agent, degarelix, has proved to provide rapid testosterone suppression without the initial testosterone surge associated with luteinizing hormone-releasing hormone agonists. Other new agents in early development include a selective and irreversible inhibitor of CYP17, abiraterone, which has shown success in patients with castration-resistant metastatic prostate cancer, and MDV3100, a novel small molecule that acts as an oral nonsteroidal antiandrogen agent. In sum, these latest agents might lead to a paradigm shift in the treatment of patients with advanced prostate cancer; however, additional studies are required to clarify the many questions that remain regarding the optimal use and sequence of these agents. © 2011 Published by Elsevier Inc.
News Article | December 14, 2016
- GEN-003 Phase 2b placebo-controlled clinical efficacy data six months after dosing expected in January 2017 - - Announced new research collaborations with Checkmate Pharmaceuticals in advanced melanoma and US Oncology Research across multiple cancers - CAMBRIDGE, Mass., Dec. 14, 2016 (GLOBE NEWSWIRE) -- Genocea Biosciences, Inc. (NASDAQ:GNCA), a company developing T cell-directed vaccines and immunotherapies today held its first R&D day for investors and analysts. The company highlighted its lead program, GEN-003, a T cell-directed immunotherapy for the treatment of genital herpes infections for which six-month Phase 2b placebo-controlled clinical efficacy is expected in January 2017. The Company also introduced its immuno-oncology strategy, including its plans to file an IND for a neoantigen cancer vaccine in 2017 and announced new research collaborations with Checkmate Pharmaceuticals, Inc. (Checkmate) and US Oncology Research. “Genocea is a leader in the development of innovative therapies at the forefront of the T cell revolution with GEN-003 for genital herpes and our emerging work in immuno-oncology,” said Chip Clark, president and chief executive officer of Genocea. “We believe that ATLASTM, our T cell antigen discovery platform, that is the basis of our clinical success to date in infectious diseases, is ideally suited to advance the understanding of the role T cells play in killing cancer. Our confidence in our immuno-oncology programs is strengthened by the collaborations we announced today, which reflect broad interest in our unique ability to comprehensively profile a person’s actual T cell responses to cancer.” Today, Genocea highlighted the significant body of clinical data it has generated over the course of three clinical trials for what may be the first new therapy for genital herpes in more than 20 years. GEN-003 is a first-in-class T cell-directed immunotherapy designed to elicit both a T cell and B cell immune response to antigens prioritized using the ATLAS platform. Genocea's ATLAS platform profiled the comprehensive spectrum of actual T cell responses mounted by humans in response to their genital herpes disease to identify the antigen targets that drove protective T cell responses. Based on clinical data to date, as well as market research showing the significant dissatisfaction among patients with current treatment options for genital herpes, GEN-003 may offer patients an important new treatment option with the promise of improved ‘real-world’ clinical outcomes and sustained reductions in viral shedding with the convenience of annual maintenance dosing. The Company expects to report six-month clinical efficacy data from its ongoing Phase 2b placebo-controlled trial in January 2017. Guest speaker Nicholas Van Wagoner, M.D., Ph.D., Assistant Professor, Division of Infectious Diseases at the University of Alabama, Birmingham, School of Medicine provided an overview of the disease and reviewed the current treatment approach for genital herpes and affirmed his belief that a product with the profile of GEN-003 could create a much-needed additional treatment option for patients and physicians. Genocea also today for the first time presented the results of extensive new market research based on GEN-003’s demonstrated clinical profile, suggesting that patients, physicians and payers all view GEN-003 favorably. Mr. Clark presented data demonstrating the Company’s belief that GEN-003 could have upwards of $2 billion global revenue potential if successfully developed worldwide. Guest speaker Charles G. Drake, M.D., Ph.D., Director of GU Medical Oncology, Co-Director: Immunotherapy Program, Associate Director for Clinical Research, and Professor of Oncology and Immunology at the Herbert Irving Cancer Center at Columbia University, provided an overview of immunotherapy in cancer. His presentation reviewed the progress made in treating cancer with checkpoint inhibitors and the opportunity to further improve clinical outcomes, including through a better understanding of which patients will benefit from existing therapies and combining checkpoint inhibitors with cancer vaccines. A Genocea presentation followed, introducing its immuno-oncology strategy and highlighting the unique ability of its ATLAS platform to comprehensively elucidate the T cell responses that patients make to cancers. This capability is currently being applied to profiling T cell responses of patients who are treated with checkpoint inhibitors and other immune modulators, with the goal of finding signatures of T cell response that associate with positive and negative outcomes. Genocea plans to use these insights to help prospectively define, in a commercial or clinical setting, patients who could benefit from these therapies. Genocea is also advancing a personalized neoantigen cancer vaccine program toward the filing of an Investigational New Drug (IND) application in 2017. This program leverages Genocea’s deep vaccinology experience along with ATLAS’s differentiated ability to select vaccine antigens based on an individual’s comprehensive T cell responses to the mutations in their own cancer. The company believes that ATLAS overcomes the weaknesses of conventional algorithm approaches to cancer antigen selection, which have significant false positive prediction rates. The company also updated progress on the development of a vaccine for cancers associated with Epstein Barr Virus (EBV). ATLAS screening has already identified novel T cell antigens, including those which appear to be associated with natural immunity against EBV infection and antigen selection and prioritization is ongoing. This morning, the Company announced a research collaboration with Checkmate to characterize patterns of T cell responses to tumor-associated antigens in advanced melanoma. The goal of the collaboration is to identify the specificity and characteristics of T cells associated with protective T cell responses to potentially optimize clinical development and ultimately, clinical practice with CMP-001. ATLAS will be used to profile the T cell responses of approximately 20 patients enrolled in Checkmate’s ongoing Phase 1b clinical trial of CMP-001 in combination with the checkpoint inhibitor pembrolizumab to a library of tumor-associated antigens common to patients with advanced melanoma. The T cell response signatures of those patients who respond to CMP-001 / pembrolizumab combination therapy will be compared to the signatures of those who do not respond, thereby potentially identifying antigens associated with positive or negative patient outcomes. Genocea also announced this morning a new collaboration with US Oncology Research, one of the USA's largest research programs specializing in oncology clinical trials, to screen the T cell responses of cancer patients with solid tumors who will be treated with checkpoint inhibitors against the complete repertoire of patient-specific putative cancer neoantigens. The objective of the collaboration is to use ATLAS to further Genocea’s expertise in identifying signatures of T cell responses in cancer patients and to discover new T cell cancer vaccine antigens. A replay of the R&D day can be accessed at: http://ir.genocea.com/events.cfm. About ATLAS ATLAS is a first of its kind proprietary rapid antigen identification screening system designed to find targets of protective T cell responses. The technology solves challenges to date associated with finding targets of T cell responses. ATLAS can examine T cell responses from large, diverse human populations, and comprehensively screen every potential antigen from a pathogen or cancer in a rapid, high-throughput manner, taking weeks versus years to find relevant antigens. Because targets identified by ATLAS are based on actual human immune responses to all potential antigens, with no guesswork or predictions, by the time these candidates reach clinical trials there may be a greater likelihood of success in clinical development. This approach provides the ability to identify smarter targets for use in developing vaccines and immunotherapies to treat infectious disease, cancer and autoimmunity. About Genocea Genocea is harnessing the power of T cell immunity to develop life-changing vaccines and immunotherapies. T cells are increasingly recognized as a critical element of protective immune responses to a wide range of diseases, but traditional discovery methods have proven unable to identify the targets of such protective immunity. Using ATLASTM, its proprietary technology platform, Genocea identifies these targets to potentially enable the rapid development of medicines to address critical patient needs. Genocea’s pipeline includes GEN-003, a novel T cell-enabled immunotherapy for genital herpes in Phase 2 clinical development, and earlier-stage investments in immuno-oncology. For more information, please visit the company's website at www.genocea.com. Forward-Looking Statements Statements herein relating to future business performance, conditions or strategies and other financial and business matters, including expectations regarding clinical developments, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. Genocea cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks and uncertainties, including Genocea's ability to progress any product candidates in preclinical or clinical trials; the ability of ATLAS to identify promising product candidates in oncology; the scope, rate and progress of its preclinical studies and clinical trials and other research and development activities; anticipated clinical trial results; current results may not be predictive of future results; even if the data from preclinical studies or clinical trials is positive, regulatory authorities may require additional studies for approval and the product may not prove to be safe and efficacious; Genocea's ability to enter into future collaborations with industry partners and the government and the terms, timing and success of any such collaboration; risks associated with the manufacture and supply of clinical and commercial product; the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; Genocea's ability to obtain rights to technology; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility; the rate of cash utilized by Genocea in its business and the period for which existing cash will be able to fund such operation; Genocea's ability to obtain adequate financing in the future through product licensing, co-promotional arrangements, public or private equity or debt financing or otherwise; general business conditions; competition; business abilities and judgment of personnel; the availability of qualified personnel and other factors set forth under "Risk Factors" in Genocea's Annual Report on Form 10-K for the fiscal year ended December 31, 2015 and other filings with the Securities and Exchange Commission (the "SEC"). Further information on the factors and risks that could affect Genocea's business, financial conditions and results of operations is contained in Genocea's filings with the SEC, which are available at www.sec.gov. These forward-looking statements speak only as of the date of this press release and Genocea assumes no duty to update forward-looking statements.
A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma: A multicenter clinicopathologic experience and new prognostic score
Phillips A.A.,Columbia University |
Phillips A.A.,Herbert Irving Cancer Center |
Shapira I.,Hofstra University |
Willim R.D.,Herbert Irving Cancer Center |
And 13 more authors.
Cancer | Year: 2010
BACKGROUND: To define the clinicopathologic and prognostic features of patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) in North America, standard criteria were used to identify patients with ATLL. METHODS: Statistical analyses used included descriptive statistics, Kaplan-Meir survival analysis, and recursive partitioning. RESULTS: Eighty-nine patients were identified between August 1992 and May 2007, including 37 (41.6%) males and 52 (58.4%) females with a median age of 50 years (range, 22-82 years). All but 6 patients had immigrated to the United States from the Caribbean, Latin America, or Africa. The acute subtype predominated (68.5%). The majority of patients received a combination-alkylator- based chemotherapy regimen in the front-line setting (72.6%). The most common regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone at standard doses or attenuated and/or with methotrexate (CHOP-like), which produced an overall response rate of 64.1%. Despite initial responses to therapy, the median overall survival for all subtypes was 24 weeks (range, 0.9-315 weeks). Although the International Prognostic Index and Prognostic Index for peripheral T-cell lymphoma unspecified identified subsets of patients, these models were not completely predictive. A recursive partitioning analysis was performed on the data, which successfully identified 3 prognostic categories based on Eastern Cooperative Oncology Group performance status, stage, age, and calcium level at diagnosis. CONCLUSIONS: This series proposed a new prognostic model for patients with HTLV-1-associated ATLL and confirmed a poor outcome for these patients in North America. © 2010 American Cancer Society.
Hensle T.W.,Columbia University |
Deibert C.M.,Herbert Irving Cancer Center
Urologic Clinics of North America | Year: 2012
Congenital abnormalities of the genitourinary system have a definable durable impact on the adult lives of those individuals affected, despite prompt and appropriate surgical and medical intervention during infancy and childhood. Three abnormalities are described, including relatively common problems of the newborn male, such as hypospadias and cryptorchidism, as well as a less common issue, posterior urethral valves. An understanding and awareness of the consequences of these 3 congenital abnormalities is paramount for the long-term care of the pediatric patient as he transitions to adolescence and adulthood. © 2012 Elsevier Inc.
Saif M.W.,Herbert Irving Cancer Center |
Saif M.W.,Columbia University
Expert Opinion on Drug Safety | Year: 2011
Hand-foot syndrome (HFS), or palmar-plantar erythrodysesthesia, is a common side effect in patients taking long-term 5-fluorouracil treatment and is the most frequently reported side effect of oral capecitabine therapy (≥ 50% of patients). Although the pathogenesis of HFS is not fully understood, it may be due to damaged deep capillaries in the soles of the feet and palms of the hands, leading to a COX inflammatory-type reaction, or related to enzymes involved in the metabolism of capecitabine, namely, thymidine phosphorylase and dihydropyrimidine dehydrogenase. Ethnic variations in the clinical manifestation of HFS warrant further attention, and an alternative system for grading HFS in non-white patients has been proposed. In addition to treatment interruption and dose reduction, supportive treatments can help alleviate symptoms. Because capecitabine is an oral therapy administered at home, it is crucial that patients understand the importance of complying with treatment, be aware of the possibility of HFS, and inform the doctor or nurse immediately if symptoms of HFS develop. Several cases of HFS are presented. © 2011 Informa UK, Ltd.