Category Archives: Genetics

Introduction

[Note: Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.]

[Note: Many of the genes described in this summary are found in the Online Mendelian Inheritance in Man (OMIM) database. When OMIM appears after a gene name or the name of a condition, click on OMIM for a link to more information.]

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women.

Estimated new cases and deaths from CRC in 2015:[1]

About 75% of patients with CRC have sporadic disease with no apparent evidence of having inherited the disorder. The remaining 25% of patients have a family history of CRC that suggests a hereditary contribution, common exposures among family members, or a combination of both. Genetic mutations have been identified as the cause of inherited cancer risk in some colon cancerprone families; these mutations are estimated to account for only 5% to 6% of CRC cases overall. It is likely that other undiscovered genes and background genetic factors contribute to the development of familial CRC in conjunction with nongenetic risk factors.

(Refer to the PDQ summaries on Colorectal Cancer Screening; Colorectal Cancer Prevention; Colon Cancer Treatment; and Rectal Cancer Treatment for more information about sporadic CRC.)

Colorectal tumors present with a broad spectrum of neoplasms, ranging from benign growths to invasive cancer and are predominantly epithelial-derived tumors (i.e., adenomas or adenocarcinomas).

Pathologists have classified the lesions into the following three groups:

Research, however, suggests increased CRC risk in some families who have multiple members affected with juvenile polyposis, Peutz-Jeghers syndrome, and hyperplastic polyposis.[2-4]

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Genetics of Colorectal Cancer - National Cancer Institute

"Inbred" redirects here. For the 2011 British film, see Inbred (film).

Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically, in contrast to outcrossing, which refers to mating unrelated individuals.[1] By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and other consequences that may arise from incestuous sexual relationships and consanguinity.

Inbreeding results in homozygosity, which can increase the chances of offspring being affected by recessive or deleterious traits.[2] This generally leads to a decreased biological fitness of a population[3][4] (called inbreeding depression), which is its ability to survive and reproduce. An individual who inherits such deleterious traits is referred to as inbred. The avoidance of such deleterious recessive alleles caused by inbreeding, via inbreeding avoidance mechanisms, is the main selective reason for outcrossing.[5][6] Crossbreeding between populations also often has positive effects on fitness-related traits.[7]

Inbreeding is a technique used in selective breeding. In livestock breeding, breeders may use inbreeding when, for example, trying to establish a new and desirable trait in the stock, but will need to watch for undesirable characteristics in offspring, which can then be eliminated through further selective breeding or culling. Inbreeding is used to reveal deleterious recessive alleles, which can then be eliminated through assortative breeding or through culling. In plant breeding, inbred lines are used as stocks for the creation of hybrid lines to make use of the effects of heterosis. Inbreeding in plants also occurs naturally in the form of self-pollination.

Offspring of biologically related persons are subject to the possible impact of inbreeding, such as congenital birth defects. The chances of such disorders is increased the closer the relationship of the biological parents. (See coefficient of inbreeding.) This is because such pairings increase the proportion of homozygous zygotes in the offspring, in particular deleterious recessive alleles, which produce such disorders.[8] (See inbreeding depression.) Because most recessive alleles are rare in populations, it is unlikely that two unrelated marriage partners will both be carriers of the alleles. However, because close relatives share a large fraction of their alleles, the probability that any such deleterious allele is inherited from the common ancestor through both parents is increased dramatically. Contrary to common belief, inbreeding does not in itself alter allele frequencies, but rather increases the relative proportion of homozygotes to heterozygotes. However, because the increased proportion of deleterious homozygotes exposes the allele to natural selection, in the long run its frequency decreases more rapidly in inbred population. In the short term, incestuous reproduction is expected to produce increases in spontaneous abortions of zygotes, perinatal deaths, and postnatal offspring with birth defects.[9] The advantages of inbreeding may be the result of a tendency to preserve the structures of alleles interacting at different loci that have been adapted together by a common selective history.[10]

Malformations or harmful traits can stay within a population due to a high homozygosity rate and it will cause a population to become fixed for certain traits, like having too many bones in an area, like the vertebral column in wolves on Isle Royale or having cranial abnormalities in Northern elephant seals, where their cranial bone length in the lower mandibular tooth row has changed. Having a high homozygosity rate is bad for a population because it will unmask recessive deleterious alleles generated by mutations, reduce heterozygote advantage, and it is detrimental to the survival of small, endangered animal populations.[11] When there are deleterious recessive alleles in a population it can cause inbreeding depression. The authors think that it is possible that the severity of inbreeding depression can be diminished if natural selection can purge such alleles from populations during inbreeding.[12] If inbreeding depression can be diminished by natural selection than some traits, harmful or not, can be reduced and change the future outlook on a small, endangered populations.

There may also be other deleterious effects besides those caused by recessive diseases. Thus, similar immune systems may be more vulnerable to infectious diseases (see Major histocompatibility complex and sexual selection).[13]

Inbreeding history of the population should also be considered when discussing the variation in the severity of inbreeding depression between and within species. With persistent inbreeding, there is evidence that shows inbreeding depression becoming less severe. This is associated with the unmasking and eliminating of severely deleterious recessive alleles. It is not likely, though, that eliminating can be so complete that inbreeding depression is only a temporary phenomenon. Eliminating slightly deleterious mutations through inbreeding under moderate selection is not as effective. Fixation of alleles most likely occurs through Mullers Ratchet, when an asexual populations genomes accumulate deleterious mutations that are irreversible.[14]

Autosomal recessive disorders occur in individuals who have two copies of the gene for a particular recessive genetic mutation.[15] Except in certain rare circumstances, such as new mutations or uniparental disomy, both parents of an individual with such a disorder will be carriers of the gene. These carriers do not display any signs of the mutation and may be unaware that they carry the mutated gene. Since relatives share a higher proportion of their genes than do unrelated people, it is more likely that related parents will both be carriers of the same recessive gene, and therefore their children are at a higher risk of a genetic disorder. The extent to which the risk increases depends on the degree of genetic relationship between the parents: The risk is greater when the parents are close relatives and lower for relationships between more distant relatives, such as second cousins, though still greater than for the general population.[16] A study has provided the evidence for inbreeding depression on cognitive abilities among children, with high frequency of mental retardation among offspring in proportion to their increasing inbreeding coefficients.[17]

Children of parent-child or sibling-sibling unions are at increased risk compared to cousin-cousin unions.[18]

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Inbreeding - Wikipedia, the free encyclopedia

Seattle Genetics is up in after-hours trading after posting record sales for its blood cancer drug Adcetris, and raising guidance for the year. The biotech sold $48 million worth of Adcetris in the U.S. and Canada, a 32% year-over-year increase.

Seattle Genetics also booked $8 million worth of royalty revenue from sales of Adcetris by its overseas partner Takeda . The drug is now approved in 47 countries, including 11 new approvals in the last 12 months.

In the U.S., the big driver of sales is coming from off-label use treating Hodgkin lymphomato knock back the lymphoma so patients can get a stem cell transplant. Adcetris is currently only approved to treat Hodgkin lymphomapatients that have failed a stem cell transplant, so Seattle Genetics can't promote it for use before stem cell transplants, even if doctors are choosing to use it then.

On the back of a strong third quarter, Seattle Genetics raised its guidance for sales of Adcetris this year to between $172 million and $177 million. That guidance implies fourth-quarter sales of $40 million to $45 million.

If you're playing along at home, you'll notice that's less than the $48 million in the third quarter. The holiday season will result in less shipping days, which will affect sales; but it doesn't necessarily mean that demand is down. The aforementioned off-label sales could also diminish -- they tend to be lumpy as doctors explore what's working. And, of course, there's a good chance that management is just sandbagging its guidance.

Looking forward, Adcetris sales growth should come fromconsolidation therapy immediately following an autologous stem cell transplant in patients with Hodgkin lymphoma. Using it on all patients -- not just those who have failed a stem cell transplant -- will obviously increase sales.

Seattle Genetics recently presented top-line data for a trial in that indication, which showed Adcetris significantly extended survival without the lymphoma progressing, referred to as progression-free survival. We'll get more data on the trial at the American Society of Hematology meeting in December, where Seattle Genetics expects to have data presented at eight oral presentations. The company plans to submit an application to the FDA in the first half of 2015 for using Adcetris as a consolidation therapy, which would put it on track for an approval toward the end of next year or in early 2016.

Of course, Seattle Genetics is more than just Adcetris. The drug is built on its antibody drug conjugate technology, which the biotech has licensed to 12 different companies, including Genmab , which signed up for a second collaboration in September. During the quarter, three of the collaborators -- GlaxoSmithKline , Takeda , and Bayer -- moved drugs along in the clinic, triggering milestone payments.

Seattle Genetics isn't profitable yet; but with $340 million in cash and investments, solid growth in sales of Adcetris, and potential for future royalties from collaborators' drugs, the biotech looks like it's in good shape for now.

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Excerpt from:
Seattle Genetics, Inc. Posts Record Adcetris Sales

LOS ANGELES--(BUSINESS WIRE)--

Life Stem Genetics Inc., an emerging innovator in the advancement of Adult Stem Cell therapy, is pleased to announce that Matthew Sullivan, COO of global heath products company Asana International, and Shahab Bakhtyar, an independent medical business consultant with global experience, have joined Life Stems Executive Advisory Board.

Established earlier this year, the Executive Advisory Board has become a cornerstone of Life Stems global stem-cell growth model by actively retaining influential business leaders with broad backgrounds in corporate development and finance in our targeted industries with a focus on business expansion into Canada, Europe, Asia, and the Middle East.

Matthew Sullivan, BA, MBA, is a corporate finance specialist who has worked with numerous early-stage and well-established companies in operations as well as strategic and financial planning. Matthews background is in venture capital and business analysis. His role has ranged from business planning/implementation, M&A, market analysis to operational implementation. He is currently COO of Asana International, a global health products company, CFO of Kat Gold Holdings, a publicly traded gold production and exploration company based in Ghana, and CFO of Travelvu, a business that places smart devices in hotel rooms. Matthew holds a Bachelor of Arts degree from the University of British Columbia, Canada, and an MBA from Dalhousie University, Canada.

Shahab Bakhtyar, MBA, is an independent business consultant with a focus on expansion and financing of small to medium sized businesses. In the last 15 years, Mr. Bakhtyars consultancy has focused mainly on Western Canada where he includes medical/health service providers among his clientele. Prior to establishing his business in Canada, Mr. Bakhtyar worked in Dubai, UAE. Included among his clients were Emirate Air and FIFA to whom he provided marketing and advertising services. Mr. Bakhtyar holds an MBA from Queens University, Canada. He has traveled to over 63 countries and maintains a strong international network of business contacts with a focus throughout the Middle East and Canada.

The addition of Matthew and Shahab to our advisory board aligns with our goal of developing a team of advisors who share our core values and can help us attain our growth initiatives in the rapidly advancing Adult Stem Cell therapy business sector, says Gloria Simov, president and CEO of Life Stem Genetics. Life Stem will greatly benefit from the depth of industry expertise and overall business acumen that both Matthew and Shahab bring, and we look forward to their value-added contributions as we continue to build our base of stem cell clinics throughout the world.

About Life Stem Genetics

Life Stem Genetics (LSG) is a progressive healthcare company focused on Adult Stem Cell (ASC) healing therapies. For decades, stem cells have been utilized in the successful treatment of a variety of ailments. Today, advanced ASC therapies are being offered to patients as an efficient and painless alternative treatment for a wide range of ailments including, but not limited to, orthopedic injuries, neurological disorders such as Parkinsons and Alzheimers, cancer, arthritis, diabetes, multiple sclerosis, as well as age management. Adult Stem Cell therapies and LSGs proprietary techniques are experiencing some of the best results in the industry in helping to repair or reprogram damaged or diseased tissues and organs. Life Stems ASC specialist has performed thousands of stem cell treatments including some of the top names in PGA golf, NFL football, NBA basketball, and Major League Baseball. LSG will offer its proprietary treatments through a series of affiliate doctors and medical clinics with 60 affiliated clinics thus far. LSGs mission is to develop a comprehensive approach to the treatment and maintenance of diseases while breaking free from the medical insurance maze by tapping into an affordable private-pay sector.

Contrarian Press, the publisher, has been engaged by Life Stem Genetics to assist with identification of potential market participants who may be interested in learning more about the company and its securities. Updated disclaimer and disclosure information is available at the publisher's website listed above and at the following link:

http://www.contrarianwealthcoalition.com/guide/LIFS.pdf

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Life Stem Genetics Strengthens Its Executive Advisory Board by Adding MBAs Matthew Sullivan and Shahab Bakhtyar

LOS ANGELES--(BUSINESS WIRE)--

Life Stem Genetics (LIFS) is pleased to announce that it has completed and received the first $500,000 of the recently announced $1mm Private Placement. Our company is very happy to receive the first half of our recent private placement and hopes to close the additional $500,000 in the coming weeks.

The money will be used to attract additional affiliate offices country wide and to invest in various areas of research and development in moving our company's plans forward.

About Life Stem Genetics

Life Stem Genetics (LSG) is a progressive health care company that focuses on healing with a patients own Stem Cells. Stem Cells for years have been known to heal a variety of ailments successfully and now it is being offered as an efficient and painless way to treat many different illnesses ranging from orthopedic injuries, neurological disorders such as Parkinsons and Alzheimers, Cancer, Plastic Surgery, Age Management, Arthritis, Diabetes, Cardiology, COPD, MS, Urology, and many more. Stem Cell Therapy and LSGs proprietary techniques have experienced some of the best results in the industry, helping to repair or re-program damaged or diseased tissues and organs.

LSGs stem cell specialist has performed thousands of stem cell treatments, including the top names in PGA golf, NFL football, NBA basketball, and Major League Baseball. LSG will offer their proprietary treatments through a series of affiliate doctors, and medical clinics, with 60 affiliated clinics so far.

LSGs mission is to create a solid comprehensive approach to the treatment and maintenance of diseases and to break free from the medical insurance world by tapping into an affordable private-pay sector delivering exceptional healthcare free from the medical insurance maze.

http://www.lifestemgenetics.com/

This press release contains "forward-looking statements" within the meaning of the "safe-harbor" provisions of the Private Securities Litigation Reform Act of 1995 that are not historical facts. These statements can be identified by the use of forward-looking terminology such as "believe," "expect," "may, could, estimates, "will," "should," "project," "plan," "seek," "intend," or "anticipate" or the negative thereof or comparable terminology, and include discussions of strategy, and statements about industry trends and the Company's future performance, operations, and products. Such statements involve known and unknown risks, uncertainties and other factors that could cause the Company's actual results to differ materially from the results expressed or implied by such statements. Such risks and uncertainties include, without limitation, market acceptance of the Company's stem cell therapy treatment program; the Company's compliance with applicable statutes and regulations: the Company's reliance on third-party contractors to provide suitable treatment facilities; the Company's ability to expand its network of participating clinics and doctors; the Company's ability to develop an effective marketing strategy; the Company's ability to control and reduce advertising and marketing costs; the Company's ability to develop and increase awareness of its brand; the Company's ability to protect its trademarks; and the success of the Company's marketing focus to patients, doctors and clinics. For a discussion of these and other risks and uncertainties see "Risk Factors" and Description of Business in the Company's public filings with the SEC. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can be no assurance that such expectations will prove to be correct. The Company has no obligation to update the forward-looking information contained in this press release.

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Life Stem Genetics is Pleased to Announce That It Has Completed the First $500,000 Private Placement of the Recently ...

Seattle Genetics (SGEN) and Agensys, a subsidiary of Astellas Pharma Inc. (ALPMY), recently announced that the former has exercised its option to co-develop one more antibody-drug conjugate (ADC), ASG-15ME, under an existing collaboration. ASG-15ME is an ADC which targets the tumor antigen SLITRK6.

Astellas has filed an investigational new drug (IND) application to the US Food and Drug Administration (:FDA) so that it can commence a phase I study with ASG-15ME.

We note that the agreement between Astellas and Seattle Genetics dates back to Jan 2007. The companies had collaborated to jointly research, develop, fund and market ADCs for cancer treatments. The companies are currently co-developing a couple of ADCs - ASG-5ME and ASG-22ME.

ADCs have lately attracted a lot of attention with major companies entering into collaborations for developing potent ADCs for cancer therapy. Seattle Genetics has collaborations with companies like Roche Holding AG's (RHHBY) Genentech for the development of ADCs.

Apart from Astellas, Seattle Genetics has ADC co-development agreements with Genmab (GNMSF) and Oxford BioTherapeutics.

Seattle Genetics sole marketed ADC product is Adcetris. Adcetris was approved by the FDA in Aug 2011 for the treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (:ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not suitable for ASCT. Adcetris was also approved for systemic anaplastic large cell lymphoma (sALCL) in treatment-experienced patients. Adcetris is also being evaluated in other indications.

Seattle Genetics carries a Zacks Rank #3 (Hold) while Astellas and Roche carry a Zacks Rank #4 (Sell). Right now, Genmab looks more attractive with a Zacks Rank #1 (Strong Buy).

Read the Full Research Report on SGEN

Read the Full Research Report on RHHBY

Read the Full Research Report on GNMSF

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SGEN/Astellas to Co-Develop Another ADC

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today highlighted multiple ADCETRIS (brentuximab vedotin) data presentations at the 12th International Conference on Malignant Lymphoma (ICML) being held June 19-22, 2013 in Lugano, Switzerland. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), that was granted accelerated approval by the FDA in August 2011 for relapsed HL and relapsed sALCL and conditional marketing authorization by the European Commission in October 2012 for relapsed or refractory HL and relapsed or refractory sALCL. Four oral and two poster presentations at ICML illustrated the broad clinical development program for ADCETRIS, including oral presentations describing the ongoing global phase 3 ECHELON-2 trial in frontline mature T-cell lymphoma (MTCL) and data from a phase 2 trial in patients with relapsed MTCL. In addition, an oral presentation included the first report of data from an investigator-sponsored trial evaluating ADCETRIS in first-relapse HL patients as part of a pre-autologous stem cell transplant regimen.

With last years European conditional marketing authorization supporting the use of ADCETRIS as a treatment for patients with relapsed HL and sALCL, this meeting provides us with an opportunity to share important ADCETRIS data with the international physician and patient community as we evaluate ADCETRIS in additional disease settings, said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. ADCETRIS is being evaluated for the treatment of CD30-positive malignancies in more than 20 ongoing clinical trials, including three global phase 3 trials. We look forward to the ongoing presentation of important data at medical meetings such as ICML, demonstrating the broad therapeutic potential of ADCETRIS.

Oral Presentations

PET-adapted Sequential Therapy with Brentuximab Vedotin and Augmented-ICE in Relapsed and Refractory Hodgkin Lymphoma (Abstract #141, oral session on Saturday, June 22, 2013 at 8:50 AM CET)

In an ongoing investigator-sponsored phase 2 clinical trial, patients with relapsed or refractory HL have been enrolled to determine whether ADCETRIS can replace the combination chemotherapy regimen ifosfamide, carboplatin and etoposide (ICE) or be used in sequential administration with ICE to increase the rate of pre-transplant FDG-PET normalization (PET-N), which is an important prognostic factor for patients undergoing autologous stem cell transplant (ASCT). At the time of data analysis, 40 patients had been enrolled and 33 patients had completed the treatment program. Key findings presented by Dr. Alison Moskowitz from Memorial Sloan Kettering Cancer Center include:

ADCETRIS is not approved for salvage HL patients who are deemed eligible for ASCT.

Safety and Efficacy of Brentuximab Vedotin for the Treatment of Relapsed Mature T-/NK-Cell Lymphomas (Abstract #152, oral session on Saturday, June 22, 2013 at 10:00 AM CET)

In an encore presentation from the 2012 American Society of Hematology (ASH) Annual Meeting, data were highlighted from a subset of patients in an ongoing phase 2 clinical trial evaluating ADCETRIS in CD30-positive non-Hodgkin lymphoma. The trial is designed to assess the antitumor activity, duration of response and safety profile of ADCETRIS in these patients. At the time of data analysis, 29 patients with MTCL had been enrolled, including 11 with angioimmunoblastic T-cell lymphoma (AITL) and 18 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The median number of prior systemic therapies in both lymphoma classifications was two. Key findings include:

ADCETRIS is not approved for the treatment of the MTCL subtypes described in this presentation.

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Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Clinical Data at International Conference on Malignant ...

LUGANO, Switzerland--(BUSINESS WIRE)--

Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (SGEN) today announced data from a post-hoc analysis examining progression-free survival (PFS) following treatment with ADCETRIS (brentuximab vedotin) versus last prior therapy in patients diagnosed with relapsed or refractory Hodgkin lymphoma (HL) post-autologous stem cell transplant (ASCT) or relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). The data were highlighted during a presentation at the 12th International Conference on Malignant Lymphoma (ICML) being held June 1922, 2013 in Lugano, Switzerland.

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL.

The post-hoc analysis compared investigator assessed PFS following ADCETRIS single-agent treatment to the last prior systemic therapy in patients taking part in two pivotal Phase 2 studies. The post-hoc analysis was conducted in patients with relapsed or refractory HL post-ASCT or relapsed or refractory sALCL in the intent-to-treat (ITT) population. It also included prior systemic treatment histories and post-ADCETRIS stem cell transplant experience for each patient in the ITT populations.

These encouraging data suggest that ADCETRIS may delay disease progression compared to prior therapies used in this heavily pretreated patient population, said John Radford, M.D., Professor of Medical Oncology, University of Manchester, Manchester, UK. ADCETRIS is a CD30-targeted treatment option for patients with relapsed or refractory HL or relapsed or refractory sALCL that has shown a high overall response rate, including durable complete responses in both of its approved indications.

Progression-free survival analyses of two pivotal phase 2 studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma (Poster #303)

The analysis, presented by Dr. Radford, included:

Relapsed or Refractory HL post-ASCT

Relapsed or Refractory sALCL

Details of the poster presentation are as follows:

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Takeda and Seattle Genetics Highlight Post-Hoc Analysis Examining Progression-free Survival with ADCETRIS® ...

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today announced the initiation of a phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with bendamustine for patients with Hodgkin lymphoma (HL) after first relapse. The multi-phase study is divided into two cohorts to determine the recommended dosing level and tolerability of combination use and to assess the complete remission rate associated with ADCETRIS in combination with bendamustine. Seattle Genetics is the leader in the field of antibody-drug conjugates (ADCs) and ADCETRIS is an ADC directed to CD30, a defining marker of classical HL. ADCETRIS is not approved for salvage HL patients who are deemed eligible for autologous stem cell transplant (ASCT).

One of the key goals of our broad ADCETRIS clinical development program is to evaluate its use in earlier lines of HL therapy. This trial will assess the ability of ADCETRIS in combination with bendamustine to induce durable complete remissions in second-line treatment of HL patients prior to transplant, said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. In this treatment setting, single-agent bendamustine has been shown to induce a high rate of remissions with limited durability. Data from an investigator-sponsored trial with single-agent ADCETRIS demonstrated encouraging activity and tolerability in this setting. This trial is designed to determine if the combination can result in durable complete remissions, potentially increasing the number of patients eligible to receive a transplant.

This phase 1/2 single-arm, open-label clinical trial will evaluate the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients after first relapse. Patients will be eligible to receive up to six cycles of ADCETRIS in combination with bendamustine followed by additional single-agent ADCETRIS for up to a total of 16 cycles. As a part of the trial design, after patients receive ADCETRIS plus bendamustine combination therapy, they have the option to pause therapy to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Bendamustine is an alkylating agent used in the treatment of chronic lymphocytic leukemias and lymphomas. The primary endpoint of the phase 1 cohort is to determine the recommended dosing level of bendamustine in combination with ADCETRIS as well as the safety and tolerability of the combination. The primary endpoint of the phase 2 cohort is to assess the complete remission rate. Key secondary endpoints include best response, duration of response and progression-free survival. The study is expected to enroll up to 50 patients at multiple centers in the United States.

At the 54th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA, encouraging data were presented from an abstract titled Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL (Abstract #3699). The investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with chemotherapy regimens or a combination of chemotherapy with or without consolidative radiation treatment.

Of the 14 evaluable patients, 12 patients (85.7 percent) had an objective response rate, including seven (50 percent) complete remissions and five (35.7 percent) partial remissions. The most common Grade 1 or 2 adverse events were peripheral sensory neuropathy (42.9 percent), acneiform rash (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent). Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent), and there were no Grade 4 adverse events. The abstract can be found at http://www.hematology.org.

More information about the phase 1/2 trial of ADCETRIS in combination with bendamustine, including enrolling centers, is available by visiting http://www.clinicaltrials.gov.

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS was granted accelerated approval by the FDA in August 2011 and approval with conditions by Health Canada in February 2013 for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

Original post:
Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with ...

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today announced the initiation of a phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with bendamustine for patients with Hodgkin lymphoma (HL) after first relapse. The multi-phase study is divided into two cohorts to determine the recommended dosing level and tolerability of combination use and to assess the complete remission rate associated with ADCETRIS in combination with bendamustine. Seattle Genetics is the leader in the field of antibody-drug conjugates (ADCs) and ADCETRIS is an ADC directed to CD30, a defining marker of classical HL. ADCETRIS is not approved for salvage HL patients who are deemed eligible for autologous stem cell transplant (ASCT).

One of the key goals of our broad ADCETRIS clinical development program is to evaluate its use in earlier lines of HL therapy. This trial will assess the ability of ADCETRIS in combination with bendamustine to induce durable complete remissions in second-line treatment of HL patients prior to transplant, said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. In this treatment setting, single-agent bendamustine has been shown to induce a high rate of remissions with limited durability. Data from an investigator-sponsored trial with single-agent ADCETRIS demonstrated encouraging activity and tolerability in this setting. This trial is designed to determine if the combination can result in durable complete remissions, potentially increasing the number of patients eligible to receive a transplant.

This phase 1/2 single-arm, open-label clinical trial will evaluate the efficacy and tolerability of ADCETRIS in combination with bendamustine in HL patients after first relapse. Patients will be eligible to receive up to six cycles of ADCETRIS in combination with bendamustine followed by additional single-agent ADCETRIS for up to a total of 16 cycles. As a part of the trial design, after patients receive ADCETRIS plus bendamustine combination therapy, they have the option to pause therapy to receive an ASCT and then resume treatment with single-agent ADCETRIS as consolidation. Bendamustine is an alkylating agent used in the treatment of chronic lymphocytic leukemias and lymphomas. The primary endpoint of the phase 1 cohort is to determine the recommended dosing level of bendamustine in combination with ADCETRIS as well as the safety and tolerability of the combination. The primary endpoint of the phase 2 cohort is to assess the complete remission rate. Key secondary endpoints include best response, duration of response and progression-free survival. The study is expected to enroll up to 50 patients at multiple centers in the United States.

At the 54th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA, encouraging data were presented from an abstract titled Brentuximab Vedotin as a First Line Salvage Therapy in Relapsed/Refractory HL (Abstract #3699). The investigator-sponsored trial was conducted to evaluate ADCETRIS as a salvage therapy for HL. Fourteen patients were evaluated for response and safety and all had relapsed or refractory HL after initial therapy with chemotherapy regimens or a combination of chemotherapy with or without consolidative radiation treatment.

Of the 14 evaluable patients, 12 patients (85.7 percent) had an objective response rate, including seven (50 percent) complete remissions and five (35.7 percent) partial remissions. The most common Grade 1 or 2 adverse events were peripheral sensory neuropathy (42.9 percent), acneiform rash (35.7 percent), AST elevation (28.6 percent) and fatigue (28.6 percent). Grade 3 adverse events were rash acneiform (7.1 percent) and urinary tract infection (7.1 percent), and there were no Grade 4 adverse events. The abstract can be found at http://www.hematology.org.

More information about the phase 1/2 trial of ADCETRIS in combination with bendamustine, including enrolling centers, is available by visiting http://www.clinicaltrials.gov.

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS was granted accelerated approval by the FDA in August 2011 and approval with conditions by Health Canada in February 2013 for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

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Seattle Genetics Announces Initiation of Phase 1/2 Trial of ADCETRIS® (Brentuximab Vedotin) in Combination with ...