Monitoring has shown rat numbers at high levels over much of Kahurangi due to beech seedfall providing more food. With more rodents to feed on, stoat numbers then surge.
Earlier this year Conservation Minister Maggie Barry announced DOC would receive $20.7 million in further operating funding for 2015/16 from the Budget for the campaign.
The 2014 Battle for our Birds campaign saw department staff carry out 27 aerial pest control operations over more than 600,000 hectares across the South Island.
Aerial 1080 predator control will target rats. Stoat numbers are reduced through their eating poisoned rodent carcasses. Possums will also be targeted in some western areas.
Ban 1080 Party member Bill Wallace said the 1080 drop is "nonsense" and "smoke and mirrors".
"They're actually doing more harm than good. Rats are going to recover the fastest.
"The rat numbers will have crashed over the winter anyway and if they haven't counted before this drop they'll claim success for what mother nature has already done and they'll place some of our endangered birds even closer to extinction."
The Kahurangi predator control is the largest operation in DOC's programme and is planned to cover about 295,000 hectares of the park and other conservation land. The pest control will be carried out in stages across the operational area as weather conditions allow.
It begins with aerial application of non-toxic baits to encourage rats and possums to eat baits containing biodegradable 1080 pesticide that will be aerially-applied some days later.
DOC Motueka Operations Manager Chris Golding said the pest control was being timed to prevent increased predator attacks on nesting native birds so more chicks could survive to increase their populations.
"Monitoring has shown rock wren and kea in Kahurangi National Park had greater nesting success following aerial 1080 predator control in 2014 compared to areas without it. Pest control that year was also carried out to curb rat and stoat plagues following a heavy beech seed fall."
In the 2014-15 breeding season, monitored rock wren at two pest control sites raised three times more chicks than at a comparison site in the park with no pest control. The following breeding season, 2015-16, the rock wren in the 1080 area produced five times more offspring than the birds in the comparison area.
In the 2015-16 breeding season, 27 per cent of monitored kea nests in the pest control area were successful in fledging chicks. This can be compared to monitoring of kea nests in areas without pest control from 2009 to 2014 which found only 2 per cent of the nests were successful.
At the request of the New Zealander Deerstalkers' Association and Game Animal Council, deer repellent will be used in 1080 cereal baits in part of the park that is a valued hunting area. It includes part of the Cobb Valley and the Peat Valley, Deep Creek, Tableland and Lower Junction areas.
When aerial 1080 bait application takes place in an area of the park, some track and road closures will occur in that area.
Sections of track in the pest control area, including parts of the Heaphy Track, will be closed for half to a full day and will reopen after DOC staff have cleared baits from tracks. Road closures will occur on the Cobb Road, Wangapeka River Road and McCallums Mill Road during bait distribution in those areas of the park.
DOC's national Battle for our Birds programme will see rodents, stoats and possums controlled by aerially-applied 1080 baits over 24 priority conservation areas over about 810,000 hectares. This will be supported by ground control methods such as traps and poison bait stations over about 70,000 hectares.


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Holy Everything: Love starts inside, but it can change the world
By Emily Carson, life@postbulletin.com
Before Jesus was born, Mary and Joseph had some major hurdles to overcome. Theirs is a tale of courage in the face of immense challenges. The roots of the Christmas story have nothing to do with trees, elves, or gift wrap (though these can certainly serve as lovely accoutrements).
Instead, at the heart of the Christmas story is one family who refused to allow the insidious nature of fear to pervade their lives. After Jesus was born, all wasn't eternal merriment and delight. Quite the contrary. Mary and Joseph lived in perplexing times! The political climate was unstable and a maniacal ruler named Herod was murdering children in the search for an infant king.
Mary and Joseph persevered. They were the epitome of resilience. From the moment they found out that she was going to birth that totally unexpected baby, Mary and Joseph clung tightly to the truth that love is stronger than fear. Even when they were living as refugees in Egypt (yes, it's true; our King of Kings spent a season of life as a toddler refugee), they held onto hope.
In spite of it all, Mary and Joseph refused to bite on to the fearful lures that were strung about them. The bait was there … they could've chosen to live in utter, constant fear. But they refused. They refused to let fear take over their brains and lives.
It's a contemporary storyline.
There are loads of toxic fear being spewed about these days. The content of the spewing: gross, disgusting, throw-up. Fear vomit. It's everywhere. Some days it feels like everywhere I look, I'm being fed lies about more things/people/ideas of which to be afraid.
Like Mary and Joseph, we, too, are being baited with fear. On the campaign trail and the morning news. In the break room. On our Facebook walls. Fear, fear, fear.
Fear is defined as "a distressing emotion aroused by impending danger, evil, pain, etc., whether the threat is real or imagined; the feeling or condition of being afraid."
We've all felt fear, and it's a consuming, overwhelming emotional state. Jesus mentions the topic a lot. And when he speaks about fear, he generally says the same thing: "Don't be afraid" (see Matthew 14:27 and John 14:27 for two examples).
Friends, hear me when I say: We're being collectively manipulated into being afraid of the wrong things! We're being fed lies about entire people groups and religions. Our own good intentions — to build communities of safety, peace, and security — are being used against us. We're being baited with the idea that in order to experience security, we need to exclude, judge, and condemn.
But that's a lie. That's a total lie. And it isn't the Gospel. In fact, this kind of exclusionary thinking is the opposite of the heart of Christmas.
I know sometimes the world appears scary and dangerous. I get it. I live here, too. But being afraid isn't a sustainable solution. When we're afraid, a whole different system in our brain takes over. We can't think logically, problem-solve, or compromise when we're afraid, and those are the kinds of things we're going to need to be able to do if we want to live in a compassionate world of justice and peace.
The same holds true whether we're talking about family conflict, immigrant legislation, or interfaith relations: Fear shuts us down, but love opens us up.
I'm not describing mushy-gushy love. I'm talking about neighborly love. The kind of love that says, "Hey, you're a human and I'm a human. And here we both are on this planet! I want the best for you, fellow human. And I trust that you want the best for me, too. Let's stop being afraid and work together." That's love!
The fear tide can turn. In fact, it is turning. There a signs of love in the face of fear all around us.
In the Old Testament book of Isaiah, God says in chapter 41, verse 10, "Fear not, for I am with you." We don't have to be afraid. In fact, we are commanded not to be afraid. Instead, we get to live in love. As Christmas draws near, may we join together in turning off whatever conjures up fear in our lives. Instead, let's turn toward the images, movies, music, and conversations which lead to love. It starts within our own hearts.
God, give us the courage you gave to Mary and Joseph, that we, too, might choose love over fear.
February arrives with a comet and some great constellations
Comet ZTF is closest to Earth in early February.
By Mike Lynch
Secondhand and simple style is Donna Unseth's go-to move
Donna is a cabinetmaker/woodworker at a local custom cabinet-making shop.
By Jeanette Caban
High seas cuisine
Food writer Holly Ebel says a cooking class on a cruise ship turned into a fantastic culinary adventure.
By Holly Ebel
'There are people waiting to encourage you. ... You just have to find them'

redpajama_set_name: RedPajamaCommonCrawl


Online application provides intuitive Web log analysis online. Requires Silverlight 4.0. Accepts multiple log files, for example from IIS and produces several aspects of web traffic by client IP, resource, date. Also shows new client IPs for every day.


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Ibadan Pillars Visit Prof. Ekanola, Demand indigene as Substantive VC.
Still in the spirit of the historic and meritorious achievement, the Indigenes of Ibadan land, under the banner of Ibadan Pillars, has on Monday expressed her candid desire for another Ibadan indigene to take over from Prof. Ekanola Adebola, the new acting Vice Chancellor of the University of Ibadan (UI) when his tenue expires.
This was disclosed during a courtesy visit to the new University of Ibadan acting Vice Chancellor, Prof. Ekanola Adebola at the Tekena Tamuno Building, where his office is situated.
In his congratulatory message and purpose of the visit, the President of the Ibadan Pillars, Asiwaju Nurudeen Akinade said in his words that
"the University of Ibadan has never had a Vice Chancellor of Ibadan origin in her 72 years of existence, but now we are glad the University community has given an Ibadan son the historical opportunity to be in an acting capacity for first time ever. Hence, our group is deeming it fit to pay one of our own a congratulatory visit in anticipation that another Ibadan son will also take over from him as the permanent Vice Chancellor."
Responding to the gesture of the visitation, the new acting Vice Chancellor, Prof Adebola Ekanola said that he is most delighted by the gesture of visit, as the category of well-meaning Ibadan indigenes deemed it fit to paying him this courtesy visit. He highlighted that he is happy that his own people are identifying with him, which will serve as a motivation for success in his tenure.
ALSO READ Eid-el-Fitri: Oyo NUJ Felicitates members, Seeks More Efforts Against COVID-19
He however promised that he will deliver the mandate well even in the short period as the University of Ibadan's Vice Chancellor.
It should be noted that this is the first time an indigene of Ibadan land is emerging as Vice Chancellor of the 72-year-old institution. Hence, Prof. Adebola Ekanola is expected to stay in office for six months in the acting capacity.
In the company of the Ibadan Pillars's President is Tpl Duro Ogunsesan, the Director, Continuing Education Center (CEC), The Polytechnic, Ibadan, Hon, Shina Alabi, former Chairman T.C.T.C, Oyo State, Chief Akinboade Ologbojo, former S.A to the Governor.
Tags: IbadanIbadan PillarsProfessor Ekanola
Miss Oyo 2020 Princess Adedoja Adeyemi Visits Alaafin
Senator Buhari Collaborates with NDE to Train Another 300 Youths on Tiling Works
NationalInsight
LAUTECH Ownership: Oyo to pay N8b to Osun in 3 Years as Asset Sharing Agreement
OAU Resumes February 7
LAUTECH ASSETS: Oyo to Pay Osun N8b


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World Cup 2022: See Who's Favored to Win it All!
By Jason KellyPublished On: 2022-11-01
Within one month, 32 countries will gather in Qatar to kick off the start of the World Cup 2022. So, let's see which countries are favored to secure the first four positions.
Who is Favored to be Champion
1. Brazil
It looks like Brazil is favored to win the World Cup. The Brazilian selection team has won six of their last six games. And five of those games were won by three or more goals. They scored a total of 22 goals and gave up just two in six games. They beat Tunisia 5-1, Ghana 3-0, Japan 1-0, South Korea 5-1, Bolivia 4-0, and Chile 4-0.
Brazil's game against Japan was their lowest-scoring and most challenging, 1-0. Neymar secured the win with a penalty shot.
Brazil has many new faces that are superior players. Also, the head coach Tite, rotates his starters because of the depth of talent on the team. He can rotate his premier players as substitutes and vice versa, which helps freshen up the games in the second half. Also, since his inception as a coach, the style of Brazil's methods, play, and techniques have also changed to keep up with the different types and speeds of the game and other teams.
France's recent results have been very unpredictable. Brazil has had a steady successful winning streak. However, France has won just one of their last six games. They suffered losses at home and away from Denmark. Furthermore, they tickled down the ranks with a loss on their hometown turf again in Paris to Croatia's National team. Although they have experienced many losses, they avoided losing ranking by one point to stay in the top tier division.
In recent World Cup history, France has fared ok. They won in 1998 and twenty years later in 2018. However, they failed to qualify for two consecutive World Cups in 1990 and 1994.
Once again, France has very high expectations. But the team's past previous performance has created a different thought in people's minds. They beat Australia 2-1 and Peru 1-0. However, the performance in these games seemed weak, swaying the favorability of winning the Cup away from Les Bleus.
France has won twice, and they are the returning champions. The odds between France and Argentina are minimally different to win, indicating that it is almost tied. So, they have a slight favor and advantage over Argentina.
3. Argentina
It is not that Argentina is a bad team. They won two World Cups in 1978 and 1986 versus Brazil's five-time champion World Cup status. However, it seems Messi is finding it difficult to be the savior to help Argentina clench victory. Argentina has a good shot. They finished as runners-up in the CONMEBOL. However, Brazil has won 43 times versus 40 tournaments played. And Brazil has outscored Argentina with 166 goals against 162.
England is set to take fourth place. However, they have not had solid and steady play over the years. For example, they lost the 2018 World Cup semi-final to Croatia 2-1. And recently, they tied Germany 3-3, lost to Italy 1-0, and suffered a blow from Hungary 4-0.
But, like always, the World Cup has many "it depends" factors. Let's see which way the wind blows, or I should say, how the heat stifles the players. It will be 122 degrees at the time of the World cup in Qatar, and that can really create game-changing scenarios. Well, maybe not for the Brazilians.
What's Next For Team USA
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The STIHL Group develops, produces and markets power tools for forestry and landscape maintenance and for the construction industry. STIHL distributes its products through its network of 38,000 Approved Dealers in over 160 countries. The Group has 32 sales and marketing subsidiaries of its own as well as more than 120 importers. STIHL has consistently been the world's top-selling chain saw brand since 1971. The STIHL product portfolio also includes Brushcutters, Linetrimmers, Blowers, Hedgetrimmers, Cut-off machines, Earth Augers, High Pressure Cleaners, safety clothing, and various accessory items.
STIHL Pty Ltd became part of the STIHL network in 1971, with responsibility for marketing and distribution in Australia and the Pacific Islands. STIHL Pty Ltd was the first subsidiary company established by the STIHL Group outside Europe, and is currently the sixth largest in annual turnover, employing around a hundred staff. STIHL Pty Ltd distribute through a network of 430 Specialist Dealers in both rural and metropolitan markets. In the main, these are retail outlets with a technical/ mechanical orientation to ensure service back-up to the STIHL product range.


Cristiane Stam, Ford New York. Photographed by Claire Corbett wearing Marco De Vicenzo multicolored jacket. Hair and Makeup by Chrisondra Boyd at Ford Artists . Fashion Editor, Patric Chauvez.
In Fashion, wearing your clothes at a rakish angle could be the height of chic. You've seen it on television, in the movies and on the runways of Paris and Milan; therefore we bring it to the streets. The on the shoulder look is quite Chic indeed. It is the perfect way to add a dose of difference to ones look. It envelops your shoulders, frame your face and create a shape that seems to add volume mimicking the avante garde.
Be chic, wear your jacket on your shoulders.


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BEP offers new currency products
New from the Bureau of Engraving and Printing are two sets—one of which honors 25 years of production at the Western Currency Facility.
The Bureau of Engraving and Printing has introduced two new products that are now available for purchase. Included are the "2016 Texas $2 Step Currency Set" and the "2016 Happy Birthday Currency Note."
Commemorating the 25 years of currency production at it Western Currency Facility in Fort Worth, Texas, the BEP's "2016 Texas $2 Step Currency Set" features two Series 2009 $2 notes from the Dallas Federal Reserve Bank with matching numerical serial numbers beginning with "2016xxxx." Each note is protected by a clear, acid-free polymer sleeve in a folder representative of Texas.
The 2016 Texas $2 Step Currency Set is $39.95 and is limited to 6,500 sets.
Featured in the "2016 Happy Birthday Currency Note" offering is a Series 2013 $1 note with a serial number beginning with "2016xxxx." The note is protected by a clear, acid-free polymer sleeve in an attractive folder.
The 2016 Happy Birthday Currency Note is $5.95.
For additional information about BEP or to purchase products, visit www.bep.gov. BEP products may also be ordered by telephone (1-800-456-3408), by fax (1-888-891-7585), or mail (Bureau of Engraving and Printing, Mail Order Sales, 515M, 14th and C Streets, SW, Washington, D.C. 20228).
This article was originally printed in Bank Note Reporter.
>> Subscribe today or get your >> Digital Subscription
More Collecting Resources
• The Standard Catalog of United States Paper Money is the only annual guide that provides complete coverage of U.S. currency with today's market prices.
• With over 22,000 listings and 13,750 illustrations, the Standard Catalog of World Paper Money, Modern Issues is your go-to guide for modern bank notes.
BEP offers free currency readers
BEP struggles with $100
BEP director Felix to retire
BEP offers its help for hurricane victims
By Robert R. Van Ryzin
BEP offers birthday note
By Bank Note Reporter Staff
New $100s give BEP trouble
"Don't count your chickens before they are hatched," warned the old folk wisdom.
New Notes Postponed by BEP
Sales of the uncirculated 2003A $2 Single Note from the Philadelphia Federal Reserve district due to go on sale June 23 were postponed by the Bureau of Engraving and Printing.
BEP Surveying New Site for Facility Relocation
$2 star note packages new from BEP
Individual $2 star notes from all 12 Federal Reserve District banks and lucky Year of the Dog $1 notes are available from the Bureau of Engraving and Printing as of Dec. 1.
More Numismatic News


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Member since: Mar 15, 2020
I am a Canadian drummer living in Toronto, Ontario. I've played professionally across the States and Canada and in the past 3 years, opened up a home studio to record with new artists at a more affordable rate.
I want to provide you with the sound you hear in your head. Nailing the tones and parts that will make your song come to life is my main goal, whether it's liv...
I want to provide you with the sound you hear in your head. Nailing the tones and parts that will make your song come to life is my main goal, whether it's live drums, percussion, or programmed drums.
I've played on numerous recordings of artists and the greatest thrill is getting an email back from them after they've heard the tracks that says "This is exactly what I was hearing!"
I have no desire to play flashy or loud if the song doesn't call for it, I only want the artist to be happy.
I specialize in Rock, Pop and R+B, though I'm comfortable in almost any situation and I'll work with your budget - Lets make some music!
Services by Andrew Scott
Drum/Percussion Recording + Programming
Lessons By Andrew Scott
Contact Andrew Scott


Please join us and help your friends and neighbors!
Your support ensures that everyone who needs hospice care will receive it, regardless of their ability to pay. Thank you for helping your friends and neighbors!


A lot of the last few months feel like a blur to me. Thanks to items going on in the background, I was focusing a significant amount of my attention to those areas. During this time, I was able to keep up with blogging and freelance writing. Unfortunately, other projects had to take a backseat. There was simply no time to develop them to the level that was required. Call me a type A individual, but I can't put partial effort into something.
Yesterday, Christina from Well, in THIS House… and I went to a networking event held by Women TIES. The luncheon included an educational program with a focus. The theme was "How to Get Companies to Pay You to Market to Your Audience" with keynote speaker Shannon Cherry.
I had met Shannon before, but not on a professional level. Her enthusiasm and helpful hints made the wheels in my head start to go a mile a minute. I drove home thinking about ways to dust the project off and twist it to something new and even more exciting. A huge thank you to Shannon and the other women in the room who are leading the way to empowering more of us to try new things, think outside of the box, and get out of our comfort zones.
Of course, I also hope to connect with more of the people that were at the event thanks to the sheet with contacts. The fun part, one of the people there was a seventh grade teacher that I had for Social Studies.
So this week I ask you, what are items that have served as sparks of inspiration in your life? I would love to hear about them and please include a link in the comments if you have written about them.


Geni.com Anthonie Rinck ; Geocities.com/sa > Stamouers > Benade Seen and added by Charmaine (Rostoll) Miles 1 May, 2016 .
No known carriers of Johann Matthias's Y-chromosome or his mother's mitochondrial DNA have taken yDNA or mtDNA tests.
A father's death date (Benade-32 died 1774) should not be more than nine months before one of his children's birth dates (Benade-102 born 25 Sep 1774) .
I'm disconnecting the father profile Johan Matthys Benade-154 born September 23, 1787 in Fayette, Georgia, United States (born more than 50 years after the birth of his son [Born 1732 in Halberstadt, Saxony-Anhalt (Germany)] from the profile of his supposed "son" Johann Matthias Benade. This is most likely a conflation of another person with the same name in the US. Johannes Tobias Benade-155 born September 7, 1806 in Pretoria, Gauteng, South Africa could not have been married to Aletta Catharina (Carsten-23) Benade on November 7, 1784 in de Caep de Groede Hoop - 20 years before his birth. He could also not realistically be the father of Benade-154 who was born 19 years earlier in the US.
Johann Matthias is 26 degrees from Amy Gilpin, 22 degrees from Joshua Slocum and 17 degrees from Henry VIII of England on our single family tree. Login to find your connection.


Juno Boyle (played by Lois Halladay), embraces an unidentified woman. The shadow of a rocking chair can be seen on one side. From the Little Theatre of the Rockies production on Sean O'Casey's "Juno and the Paycock."
Townley Town (played by John E. Courtney) and Kitty Brown (played by Florabel Houston) stand on the balcony of Mrs. Boucicault's home, dressed in formal wear. From the Little Theatre of the Rockies production of Rachel Crothers' "Let Us Be Gay." This is the same image as LTR_01_0182.
A gathering in the Seton family nursery. Seton Cram (played by Richard Henson) converses with his apparently excited wife, Laura (played by Clarice Tatman) while Susan Potter (played by Mary Manley), Nick Potter (played by Lester Rockley), Johnny Case (played by Max McCullough), and Linda Seton (played by Florabel Houston) look on. From the Little Theatre of the Rockies Production of Philip Barry's "Holiday."
The Honorable Sir Arthur Tuttington (played by Ted Skinner in age make up, a white wig and spectacles) looks down at the camera, apparently unhappy. From the Little Theatre of the Rockies production of Edward Wooll's "Libel." This is the same image as LTR_01_0067.
Mr. Simmons (played by Gene Gullette), the headmaster of a public school in England, and his wife, Laura (played by Mary Manley), in their drawing room. From the Little Theatre of the Rockies production of John van Druten's "Young Woodley."
Josef (played by Karl Adams) and a woman, both dressed in formal attire, are seated at a table set with wine glasses, a wine bottle and a tablecloth. A man, possibly the waiter (played by D. Bruce Parker) and a woman, apparently the maid, stand by. From the Little Theatre of the Rockies production of Siegfried Geyer's "Candlelight."
Portrait of John E. Courtney in old age make up.
Terry Randall (played by Florabel Houston) standing on a bed in one of the Footlights Club bedrooms while Jean Maitland (played by Katherine Ann Faulder, immediate right of Florabel) and two other women look on. From the Little Theatre of the Rockies production of George Kaufman and Edna Ferber's "Stage Door." This is the same image as LTR_01_0094.
Outdoor portrait of Sir Toby Belch (played by Harold Weiss). From the Little Theatre of the Rockies production of William Shakespeare's "Twelfth Night."
Edward Seton (played by Herbert Stahl in old age make up, standing third from left) addresses his daughter, Linda (played by Florabel Houston, far left) while others including Johnny Case (played by Max McCullough, right of Herbert), Seton Cram (played by Richard Henson), Julia Seton (played by Katharine Ann Faulder) and Ned Seton (played by John E. Courtney) look on. From the Little Theatre of the Rockies production of Philip Barry's "Holiday."
Screenwriter Robert Law (played by Harold Weiss) assists actress Susie (played by Priscilla Morrison), who is dressed in a nurse's uniform and appears to be struggling to walk in her shoes. They are watched by screenwriter J. Carlyle Benson (played by Karl Adams), cowboy actor Larry Toms (played by Julius Christensen) and two other men.
A young woman in skirt and hat poses in the front lawn of a house. She is holding a handbag. A house with a window awning and a contemporary car can be seen in the background.


All of our box beams are made from the same real Northwestern Spruce, Cedar, and White Oak that we use in our wood siding products. They provide all of the characteristics of a solid wood beam, at a fraction of the weight. We don't use thin veneers or cast polyurethane substitutions, and we believe one should never settle for faux wood beam options.
We use proprietary processes to reproduce an authentic aging process. All of our products are textured by hand, guaranteeing that no two pieces of wood will look identical. Every beam we craft is unique, and our inspiration is drawn from the wood itself.
All of our beams are custom-made for each individual client and project. In addition to our standard color and texture options, we also offer custom finishes, unfinished/raw box beams, and paint-grade options.
Many of our beam configurations are available for order directly through our website. If your desired beam options are not available for selection, please contact us for more information.
One piece Northwestern Spruce box beam lengths are available from 4' to 15'6″. For lengths longer than 15'6″, you can choose one of our joint options. All of our box beams are completely customizable to the specifications of your project. We also offer custom color matching and custom color formulations to ensure that our product is perfect for your installations.
All prices are calculated based on user-inputted customized specs on each product page. Average starting prices (listed below) are based on a 3-sided Standard texture 4"x4"x10' example beam for each color.
One piece Cedar box beam lengths are available from 4' to 15'6″. For lengths longer than 15'6″, you can choose one of our joint options. All of our box beams are completely customizable to the specifications of your project. We also offer custom color matching and custom color formulations to ensure that our product is perfect for your installations.
One piece White Oak box beam lengths are available from 4′ to 10′. For lengths longer than 10′, you can choose one of our joint options. All of our box beams are completely customizable to the specifications of your project. We also offer custom color matching and custom color formulations to ensure that our product is perfect for your installations.
We can create spans up to 24', with weight up to 512 lbs. Larger assemblies can be engineered as well. All Truss Systems are pre-assembled in the factory for easy installation, and include mounting hardware. Shop drawings are included as well.
We offer custom end caps to match your beam, available for all of our catalog colors, species, and textures, as well as for custom finish options.
Our end caps come in two variations: Standard Grain, and End Grain (extra costs apply). Our Standard Grain is designed to match the same grain patterns and texture as the face of your beam, while our End Grain option is cut from a cross-section of a solid timber, and is crafted to meet up with the grain on the face of your beam in a natural manner. Our End Grain option is currently available for custom orders only.
We offer an assortment of Corbels and Braces to accompany your beam installations. All of our aesthetic support accessories are handcrafted from solid Cedar, and feature the same colors and textures as our Cedar beam offerings. They are designed to be paired with our Cedar beams, and can be customized to your specifications. We also offer handcrafted wood pegs to complete your look. At this time, our Corbels and Braces are not available in White Oak or Northwestern Spruce.
One piece Cedar and Northwestern Spruce box beam lengths are available from 4' to 15'6″. For lengths longer than 15'6″, you can choose one of our joint options.
One piece White Oak box beam lengths are available from 4′ to 10′. For lengths longer than 10′, you can choose one of our joint options.
We also offer solid metal beam straps, in both a smooth and hammered texture, to accompany your chosen joint option. Our beam straps are also fully capable of being used with our Cedar, Northwestern Spruce, and White Oak lines. They are made-to-order to your specific dimensions, and are individually shaped for every beam.


Answers In Genesis, Mail Order Houses, listed under "Mail Order Houses" category, is located at Morris Road Leicester Leicestershire, LE2 6BR, United Kingdom and can be reached by 162708400 phone number. Answers In Genesis has currently 0 reviews.
Browse all Mail Order Houses in Leicester Leicestershire.


Promotional Screen Cleaner, Ipad Sleeve, Keyboards and Mouse.
Promotional computer items like screen cleaners, computer sleeves, mice and other practical items help reach a plugged-in audience. With so many personal computers out there, your advertisement has the potential to reach a large audience. Your custom computer accessories with your logo imprint or personalized message will play an important role in the user's work, homework or leisure Web surfing time.
Customized Round - CD opener key chain.
Universal CD / DVD opener.
Custom Bristle Buddy - Computer duster.
Did you know that every year more than 300,000,000 are sold worldwide? In the US alone, more than 80 percent of households have at least one computer, and many of those homes have more than one or even several desktop, laptop or tablet devices. With so many people using computers at both home and work, there are growing opportunities for advertisers using promotional computer items to get a message across.
plus many other items all designed to enhance the computer user's experience. A gift this practical in nature is certain to be used by the receiver, and every use will reinforce your brand or message in that user's awareness.
Promotional computer items need not cost you a fortune, either. In fact, Art Promos has numerous accessories that start at less than one dollar per unit including imprinting of your logo or personalized advertising message. It's an effective way to ensure that your logo makes in onto desks in homes and workplaces all over the place.


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EMC and Alteon Boeing Win CM RealWare Award for Best Enterprise Content Management Solution
12th Annual Intelligent Enterprise RealWare Awards Recognize Outstanding Customer IT Applications
Hopkinton, - December 20, 2004 -
EMC Corporation, the world leader in information storage and management, today announced that CMP Media's Intelligent Enterprise magazine has named EMC and its customer, Alteon, a fully owned subsidiary of The Boeing Company, as winners of the 12th Annual RealWare Awards for the best Enterprise Content Management application.
Selected by editors of Intelligent Enterprise and its sister publication, Transform , the awards recognize outstanding customer IT applications that meet strategic business objectives and deliver return on investment (ROI). RealWare Awards highlight the essential partnerships between IT solution providers, their customers, and service and system integration providers.
A subsidiary of Boeing, Alteon is the first truly global aviation training company specializing in flight and maintenance training for commercial aircraft with 100 seats or more. For Boeing to deliver an aircraft to a customer, related training manuals must be complete and adhere to all relevant Federal Aviation Administration requirements. Using the EMC Documentum Enterprise Content Management platform, Alteon developed an innovative solution to produce training manuals as needed and ship them to training locations around the world, saving valuable time and money. 10,000 page manuals that used to take many days to produce, now take about 20 minutes. Alteon estimates that the Documentum solution has paid for itself in less than 18 months, and the company is saving almost $3 million annually in system maintenance costs.
David Beyers, Business System Manager, Alteon, said, "The EMC Documentum platform has enabled us to create new training products and comply with industry regulations faster and more efficiently, while simultaneously saving Alteon millions in maintenance and other costs."
David Milam, executive vice president and chief marketing officer of EMC Software, said, "Winning a RealWare Award is especially gratifying because it rewards solutions that deliver measurable impact, like return on investment. Like Alteon, thousands of global customers rely on EMC's best-in-class enterprise content management solutions to save money, accelerate business processes, maximize operational efficiencies and comply with government and industry regulations. We're honored to share this award with such a valued customer."
About Alteon
Alteon is a wholly owned subsidiary of The Boeing Company within Boeing Commercial Airplanes' Commercial Aviation Services group, and the industry leader in providing customer-focused aviation training solutions. The training organization supports the world's aviation community with more than 70 full flight simulators and other state of the art training devices in 20 locations around the world. For more information, visit: www.flightsafetyboeing.com.
About Intelligent Enterprise
Intelligent Enterprise is the only IT publication focused exclusively on the most critical issue in business today: unlocking the value of collected information for competitive advantage. Intelligent Enterprise shows business and technology professionals how to plan, deploy, and manage the strategic applications their companies depend on to improve decision making, optimize business performance, and maximize the value of customer relationships. Published 18 times per year, Intelligent Enterprise provides comprehensive coverage of the technologies and practices that promote the collection, storage, analysis, and distribution of business information. For more information, visit: www.intelligententerprise.com. About EMC
EMC Corporation (NYSE: EMC) is the world leader in products, services and solutions for information storage and management that help organizations extract the maximum value from their information, at the lowest total cost, across every point in the information lifecycle. Information about EMC's products and services can be found at www.emc.com.


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Original Article Small Cell Lung Cancer| Volume 16, ISSUE 9, P1547-1558, September 2021
Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study
Fiona Blackhall, MD, FRCP, PhD
Fiona Blackhall
Corresponding author. Address for correspondence: Fiona Blackhall, MD, FRCP, PhD, Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom
Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
Department of Medical Oncology, The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom
Kevin Jao, MD, FRCPC
Kevin Jao
Department of Hematology and Oncology, Hopital du Sacre Coeur Montreal, Montreal, Canada
Laurent Greillier, MD, PhD
Laurent Greillier
Multidisciplinary Oncology and Therapeutic Innovations Department, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique-Hopitaux de Marseille (APHM), Aix-Marseille University, Marseille, France
Byoung Chul Cho, MD, PhD
Byoung Chul Cho
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Konstantin Penkov, MD, PhD
Konstantin Penkov
Private Medical Institution Euromedservice, St. Petersburg, Russia
Noemi Reguart, MD, PhD
Noemi Reguart
Department of Medical Oncology, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic de Barcelona, Barcelona, Spain
Margarita Majem, MD, PhD
Margarita Majem
Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Kristiaan Nackaerts, MD, PhD
Kristiaan Nackaerts
Department of Pulmonology and Respiratory Oncology, University Hospital Leuven, Katholieke Universiteit (KU) Leuven, Leuven, Belgium
Konstantinos Syrigos, MD, PhD
Konstantinos Syrigos
Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Karin Hansen, MD
Karin Hansen
Department of Oncology, Odense Universitets Hospital, Odense, Denmark
Wolfgang Schuette, MD
Wolfgang Schuette
2nd Medical Department, Krankenhaus Martha-Maria Halle-Doelau, Halle, Germany
Jeremy Cetnar, MD, MSHPR
Jeremy Cetnar
Department of Medicine, Oregon Health & Science University, Portland, Oregon
Federico Cappuzzo, MD, PhD
Federico Cappuzzo
Department of Medical Oncology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
Isamu Okamoto, MD, PhD
Isamu Okamoto
Department of Medical Oncology, Kyushu University Hospital, Fukuoka, Japan
Mustafa Erman, MD
Mustafa Erman
Department of Medical Oncology, Cancer Institute, Hacettepe University, Ankara, Turkey
Seppo W. Langer, MD, PhD
Seppo W. Langer
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Terufumi Kato, MD
Terufumi Kato
Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan
Harry Groen, MD, PhD
Harry Groen
Department of Pulmonary Disease, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Zhaowen Sun, PhD
Zhaowen Sun
AbbVie, Inc., North Chicago, Illinois
Yan Luo, MD, PhD
Yan Luo
Poonam Tanwani, BSc
Poonam Tanwani
Laura Caffrey, BSc
Laura Caffrey
Philip Komarnitsky, MD, PhD
Philip Komarnitsky
Niels Reinmuth, MD, PhD
Niels Reinmuth
Thoracic Oncology Department, Asklepios Fachkliniken München-Gauting, Gauting, Germany
Open AccessPublished:February 16, 2021DOI:https://doi.org/10.1016/j.jtho.2021.02.009
Previous ArticleApatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706)
Next ArticleA Phase 1–2 Study of Rovalpituzumab Tesirine in Combination With Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Extensive-Stage SCLC
DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated.
The TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS).
Patients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6.3 months (5.6–7.3) in the Rova-T arm and 8.6 months (7.7–10.1) in the topotecan arm (hazard ratio, 1.46 [95% confidence interval: 1.17–1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports.
Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population.
Small cell lung cancer
Rovalpituzumab tesirine
Delta-like protein 3
SCLC represents approximately 15% of all lung cancers.
Cancer facts & figures 2019.
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html
SCLC arises from epithelial cells with neuroendocrine differentiation and is molecularly and clinically distinct from other lung cancers.
Gazdar A.F.
Bunn P.A.
Minna J.D.
Small-cell lung cancer: what we know, what we need to know and the path forward.
Nat Rev Cancer. 2017; 17: 765
The Veterans Administration Lung Study Group stages SCLC as limited or extensive. The former is defined as a disease limited to the chest that can be encompassed by a radiation field and is treated with curative intent using combined modality chemoradiotherapy, or surgery and chemotherapy. The extensive-stage disease includes all other cases and accounts for approximately two-thirds of newly diagnosed patients. The preferred combination regimens for first-line treatment of extensive-stage SCLC (ES-SCLC) include a platinum agent, etoposide, and a programmed death-ligand 1 (PD-L1) inhibitor followed by maintenance treatment with a PD-L1 inhibitor.
NCCN clinical practice guidelines in oncology: small cell lung cancer v2.2021.
https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
Date accessed: March 6, 2021
Although approximately 60% to 70% of patients respond to the initial combination of anti–PD-L1 blockade and platinum-based chemotherapy, most responses are not durable, and the median overall survival (OS) is only 12 to 13 months.
Horn L.
Mansfield A.S.
Szczesna A.
First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer.
N Engl J Med. 2018; 379: 2220-2229
Paz-Ares L.
Dvorkin M.
Chen Y.
Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial.
Options for patients with relapsed or recurrent SCLC are limited.
The topoisomerase I inhibitor topotecan has global approvals for patients with SCLC with platinum-sensitive disease who progressed 60 or more days after completion of first-line chemotherapy
Novartis Pharmaceuticals Corporation. Hycamtin (Topotecan) prescribing information. https://www.novartis.us/sites/www.novartis.us/files/hycamtin_caps.pdf. Accessed March 11, 2021.
; however, its activity is limited, with a median OS of less than 6 months,
Ardizzoni A.
Hansen H.
Dombernowsky P.
Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group.
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von Pawel J.
Schiller J.H.
Shepherd F.A.
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O'Brien M.E.
Ciuleanu T.E.
Tsekov H.
Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer.
and hematologic toxicity is substantial.
Armstrong D.K.
Spriggs D.
Levin J.
Poulin R.
Lane S.
Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and SCLC: an integrated analysis.
Oncologist. 2005; 10: 686-694
Therefore, a considerable unmet need exists for the second-line treatment of SCLC.
DLL3 is an atypical Notch receptor family ligand that is expressed on the surface of tumor cells in greater than 80% of SCLC and neuroendocrine carcinoma cases but is virtually undetectable in normal adult tissue.
Saunders L.R.
Bankovich A.J.
Anderson W.C.
A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.
Sci Transl Med. 2015; 7: 302ra136
Thus, DLL3 is a potentially promising target for an antibody-drug conjugate in SCLC. Furthermore, DLL3 expression prechemotherapy and postchemotherapy seems to be consistent over time, suggesting that treatment does not interfere with DLL3 expression.
Farago A.
Isse K.
Drapkin B.
P3.12-02. Dynamics of DLL3 and ASCL1 expression in SCLC over disease course.
J Thoracic Oncol. 2018; 13: S970-S971
Rovalpituzumab tesirine (Rova-T) is a first-in-class antibody-drug conjugate composed of a DLL3-targeting immunoglobulin G1 monoclonal antibody tethered to pyrrolobenzodiazepine (PBD), a toxic DNA crosslinking agent, by means of a protease-cleavable linker.
Rudin C.M.
Pietanza M.C.
Bauer T.M.
Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study.
Lancet Oncol. 2017; 18: 42-51
In a first-in-human phase 1 study, Rova-T exhibited encouraging activity in recurrent SCLC, achieving a 31% and 85% confirmed objective response rate (ORR) and clinical benefit rate (CBR), respectively, on the basis of a central review, with a median OS of 5.8 months, in patients whose tumors expressed DLL3 in ≥50% of cells (on the basis of an anti-DLL3 mouse antibody immunohistochemistry [IHC] assay).
The phase 2 TRINITY study evaluated Rova-T in patients with DLL3-expressing SCLC that recurred after 2 or more systemic chemotherapy regimens. In contrast to the observations from the phase 1 study, Rova-T activity was modest in TRINITY, with a confirmed ORR of 12.4% (per central radiographic assessment) and a median OS of 5.6 months in all patients, and a confirmed ORR of 14.3% and a median OS of 5.7 months in a subset of DLL3-high patients (defined as ≥75% of DLL3-positive tumor cells using a rabbit anti-DLL3 antibody).
Morgensztern D.
Besse B.
Greillier L.
Efficacy and safety of rovalpituzumab tesirine in third-line and beyond patients with DLL3-expressing, relapsed/refractory small-cell lung cancer: results from the phase II TRINITY study.
Clin Cancer Res. 2019; 25: 6958-6966
In this study (TAHOE), we evaluated the efficacy and safety of Rova-T compared with topotecan in the second-line setting among patients with DLL3-high advanced or metastatic SCLC.
Study Design and Patients
The TAHOE study was an open-label, two-is-to-one randomized, phase 3 study comparing the efficacy and safety of Rova-T and topotecan in patients at least 18 years old with histologically or cytologically confirmed, advanced, or metastatic, DLL3-high SCLC with first disease progression during or after first-line platinum-based chemotherapy. Patients with a history of central nervous system (CNS) metastases were required to have a radiographically confirmed stable or improved status of active CNS disease before randomization, assessed at least 2 weeks after completion of definitive treatment (surgical resection, whole-brain radiation therapy, or stereotactic radiotherapy) and at least 4 weeks after previous radiographic assessment, off or on a stable dose of corticosteroids. No radiographic evidence of progression of definitively treated CNS disease was to be present at the baseline tumor assessment.
Additional eligibility criteria included measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Eastern Cooperative Oncology Group performance status (PS) of 0 or 1, and adequate hematological, hepatic, and renal function. The key exclusion criteria were the following: (1) clinically substantial pulmonary disease, cardiac or neurologic disorder; (2) current occurrence or previous history of grade 2 or higher pleural or pericardial effusions with an ongoing requirement for pericardiocentesis or thoracentesis (given the occurrence of Rova-T–associated effusions in previous studies); (3) a history of capillary leak syndrome; (4) known leptomeningeal metastases; (5) another invasive malignancy in the previous 2 years; (6) more than 1 previous systemic therapy regimen for SCLC; (7) lack of adequate washout from previous anticancer therapy; or (8) previous exposure to a PBD- or indolinobenzodiazepine-based drug, Rova-T, or topoisomerase I inhibitor.
The primary end point was OS. The secondary end points included: (1) progression-free survival (PFS); (2) ORR; (3) CBR; (4) duration of response (DOR); and (5) patient-reported outcomes using the physical functioning domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) questionnaire
Groenvold M.
Petersen M.A.
Aaronson N.K.
The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care.
Eur J Cancer. 2006; 42: 55-64
(quality of life questionnaire for palliative care of patients with cancer) after 6 weeks of treatment (cycle two, d 1 for Rova-T and cycle three, d 1 for topotecan) and after the final visit.
The study was performed in accordance with the 2013 Declaration of Helsinki. All patients provided informed consent before screening procedures. The study design was approved by the institutional review board or ethics committee of participating institutions. An independent data monitoring committee (IDMC) periodically reviewed the safety and efficacy data. The study is registered with ClinicalTrials.gov (NCT03061812).
Archived or fresh tumor material for DLL3 testing was collected after informed consent and before randomization. Eligibility required high DLL3 expression, which is defined as ≥75% tumor cells staining positive according to an IHC assay performed at a designated central laboratory using the DLL3 rabbit antibody Ventana SP347 (Ventana Medical Systems). Randomization (2:1) to Rova-T or topotecan was performed within 28 days of screening and was stratified through the following: (1) a previous history of brain metastases (yes versus no); (2) previous prophylactic cranial irradiation (PCI) (for patients with no previous history of brain metastases; yes versus no); (3) sensitivity to first-line platinum-based regimen (objective response or stable disease after first-line therapy and progression or recurrence-free interval ≥90 d versus progressive disease [PD] as the best response, or <90 d progression or recurrence-free interval); (4) and lactate dehydrogenase (LDH) level (>upper limit of normal [ULN] versus ≤ULN) at the screening.
Rova-T was administered intravenously (IV) at a dose of 0.3 mg/kg on day 1 of a 42-day cycle for two cycles. Dose interruptions or reductions were permitted for patients who exhibited treatment-related toxicities. Dexamethasone was coadministered orally twice daily at a dose of 8 mg on day −1, day 1, and day 2 of each cycle. Two additional cycles of Rova-T after disease progression were permitted for patients who had achieved stable disease or better, tolerated the initial treatment, did not progress for at least 12 weeks after the second dose, had not received additional anticancer therapy, and had not experienced clinically substantial symptoms related to disease progression or decline in PS. Topotecan was administered IV over 30 minutes at a dose of 1.5 mg/m2 on days 1 through 5 of a 21-day cycle. Lower doses of topotecan were permitted if required per the local label. Treatment was continued until PD unless earlier discontinuation was warranted.
Radiographic assessment by computed tomography or magnetic resonance imaging was performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until PD or death. Patients discontinuing for reasons other than PD were followed up every 6 weeks until PD, initiation of a new anticancer therapy, or death. Response criteria were assessed by the investigator using RECIST v1.1. Treatment-emergent adverse events (TEAEs) were summarized using the Medical Dictionary for Regulatory Activities, version 19.1 and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.
Sample Size and Analyses
The target sample size was estimated to be 600 patients to reach approximately 489 deaths needed to detect a 25% reduction in the risk of death (corresponding to a hazard ratio [HR] of 0.75) with Rova-T versus topotecan at a one-sided significance level of 0.025 and a power of 85%. After their fourth safety review on December 4, 2018, the IDMC recommended that enrollment be discontinued because OS with Rova-T was shorter than that of topotecan. No new patients were enrolled after December 4, 2018 per IDMC recommendation; the already enrolled patients deriving treatment benefits could complete their assigned treatment. The last visit of the last patient (end-of-treatment visit) occurred on February 12, 2020, after which the database was locked. Data are reported as of February 12, 2020, and the target sample size was not reached. Of the 287 dosed patients at data cutoff, 174 (61%) had received 2 or more doses of Rova-T and completed the regimen, and 113 (39%) had received 1 dose of Rova-T.
Efficacy analyses were performed in all randomized patients. OS was defined as the time from randomization to death from any cause. For patients who were alive, data were censored at the last date they were documented to be alive. Patients with no postbaseline information were censored at the date of randomization plus 1 day. PFS was defined as the time from randomization to the first occurrence of investigator-assessed disease progression or death from any cause. DOR was defined as the time between first response (complete response [CR] or partial response [PR], whichever was recorded first) to first documented tumor progression (assessed as per RECIST v1.1) or death owing to any cause, whichever came first. The median OS, PFS, landmark OS and PFS rates, and DOR were estimated using the Kaplan-Meier method. HR was determined using a stratified Cox proportional hazards model with treatment and stratification factors as covariates. For PFS and DOR, patients without disease progression or death were censored at the time of the last radiographic assessment. ORR included confirmed CR and PR on the basis of RECIST v1.1, from randomization until disease progression or death. CBR included CR, PR, and stable disease (on the basis of RECIST v1.1) from randomization until disease progression or death. Patients who did not meet CR or PR, including those who did not have postbaseline radiologic assessments, were considered nonresponders. TEAEs were defined as AEs with onset or increase in severity after the first dose of study drug but no more than 70 days after the last dose of study drug.
Patient-reported outcomes were collected using the EORTC QLQ-C15-PAL and the five-level EQ-5D (EQ-5D-5L) questionnaires at follow-up visits. The change from the baseline of the items and domains of the QLQ-C15-PAL were summarized by treatment arm. The change from baseline of the EQ-5D-5L utility score and visual analog scale were also summarized by treatment arm.
Baseline Characteristics and Patient Disposition
A total of 711 patients were screened between April 11, 2017 and December 7, 2018, and 444 (62%) meeting high DLL3 expression and other inclusion criteria were enrolled and randomized to Rova-T (n = 296) or topotecan (n = 148) (Fig. 1). Demographic and baseline characteristics were balanced between treatment arms and are summarized in Table 1. The median age was 64 years (range: 32–85), 277 patients (62%) were men, and 265 patients (64%) had an Eastern Cooperative Oncology Group PS of 1. Most patients (n = 339; 77%) had extensive disease at diagnosis.
Figure 1TAHOE CONSORT diagram. Rova-T, rovalpituzumab tesirine.
Table 1Patient Demographics and Baseline Characteristics
Rova-T
Median age (range), y 63.0 (36–85) 64.0 (32–85)
Male, n (%) 191 (65) 86 (58)
ECOG PS, n (%)
0 95 (33) 53 (41)
1 191 (67) 74 (57)
2 1 (0.3) 2 (2)
Missing 9 19
VALG stage at initial diagnosis, n (%)
Extensive disease 224 (76) 115 (78)
Limited disease 69 (24) 32 (22)
Missing 3 1
Response to first-line platinum-based chemotherapy, n (%)
PD 155 (52) 79 (53)
Objective response or stable disease 141 (48) 69 (47)
Lactate dehydrogenase, n (%)
>ULN 149 (50) 74 (50)
≤ULN 147 (50) 74 (50)
History of brain metastases,
Patients with a history of CNS metastases had received definitive treatment for CNS disease and were required to have no active CNS disease before randomization.
n (%)
Yes 175 (59) 87 (59)
No 121 (41) 61 (41)
Previous PCI,
Previous PCI is only conducted in patients without any history of brain metastases; percentages are calculated out of the number of patients without any history of brain metastases.
Yes 3 (2) 3 (5)
DLL3 expression level
High DLL3 expression is defined as having ≥75% tumor cells staining positive using the Ventana DLL3 (SP347) (Ventana Medical Systems) immunohistochemistry assay.
0 to <25% 0 0
25% to <75% 0 0
≥75% 296 (100%) 148 (100%)
CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; PCI, prophylactic cranial irradiation; PD, progressive disease; PS, performance status; Rova-T, rovalpituzumab tesirine; ULN, upper limit of normal; VALG, Veterans Administration Lung Study Group.
a Patients with a history of CNS metastases had received definitive treatment for CNS disease and were required to have no active CNS disease before randomization.
b Previous PCI is only conducted in patients without any history of brain metastases; percentages are calculated out of the number of patients without any history of brain metastases.
c High DLL3 expression is defined as having ≥75% tumor cells staining positive using the Ventana DLL3 (SP347) (Ventana Medical Systems) immunohistochemistry assay.
As of data cutoff in February 12, 2020, the median time on Rova-T was 12 weeks (range: 6–108), and the median number of cycles completed was 2 (1–4). A total of 178 patients (60%) discontinued Rova-T owing to the following primary reasons: (1) PD per RECIST v1.1 (n = 95; 32%); (2) AEs not related to disease progression (n = 38; 13%); (3) patient withdrawal (n = 12; 4%); (4) study termination by sponsor (n = 3; 1%); and (5) other reasons (n = 30; 10%). Eighteen patients (6%) had a dose reduction of Rova-T, with the reasons for dose reduction being AEs (n = 18; 6%) and other reasons (n = 1; 0.3%).
The median time on topotecan was 17 weeks (range: 6–79), and the median number of cycles completed was 4 (range: 1–22). A total of 128 patients (86%) discontinued topotecan primarily because of the following: (1) PD per RECIST v1.1 (n = 65; 44%); (2) AEs not related to disease progression (n = 26; 18%); (3) patient withdrawal (n = 15; 10%); (4) study terminated by sponsor (n=2; 1%); (5) lost to follow-up (n = 1; 1%); and (6) other reasons (n = 19; 13%). Topotecan dose reductions occurred in 52 patients (40%), because of AEs (n = 44; 34%), logistical or scheduling problems (n = 2; 2%), or other reasons (n = 9; 7%). At cycle one day 1, 11 patients (9%) received topotecan at 1 mg/m2, a dose level lower than the protocol-defined level of 1.5 mg/m2.
After data lock (February 12, 2020), all patients discontinued from the study. The primary reasons for study discontinuation in the Rova-T arm were death (n = 259; 88%), termination by sponsor (n = 21; 7%), withdrawal by patient (n = 13; 4%), lost to follow-up (n = 2; 1%), and other (n = 1; 0.3%); those in the topotecan arm were death (n = 112; 76%), termination by sponsor (n = 18; 12%), withdrawal by patient (n = 13; 9%), and lost to follow-up (n = 5; 3%).
Following the recommendation by the IDMC to discontinue study enrollment, the data collection plan was minimized, and statistical testing for efficacy end points was not performed as originally planned. For efficacy end points that did have enough data to implement the statistical models, results were descriptively summarized by treatment arms.
After a median follow-up of 8.3 months (range: 0.03–32.1), 262 patients (86%) in the Rova-T arm and 115 patients (78%) in the topotecan arm had died. The median OS (primary end point) was 6.3 months (95% confidence interval [CI]: 5.6–7.3) in the Rova-T arm and 8.6 months (95% CI: 7.7–10.1) in the topotecan arm (HR = 1.46 [95% CI: 1.17–1.82]) (Fig. 2A).
Figure 2(A) OS and (B) PFS in all randomized patients. CI, confidence interval; OS, overall survival; PFS, progression-free survival; Rova-T, rovalpituzumab tesirine.
Subgroup analysis for OS was also performed on the basis of various stratification factors (Supplementary Table 1). Similar to the observations in the overall population, a significantly shorter median OS in the Rova-T arm versus the topotecan arm was observed for patients without brain metastases at baseline, patients without previous PCI (permitted only in patients without a history of brain metastases), patients who were refractory or resistant to the first-line platinum-based regimen, patients with LDH levels greater than ULN, and patients with extensive disease at initial diagnosis. A similar trend in the median OS was observed in other subgroups, although the differences in median OS were not statistically significant. Notably, in the topotecan arm, the median OS was substantially longer in patients with LDH levels less than or equal to ULN (11.6 mo) and in patients who initially had limited disease (11.0 mo) versus the corresponding subgroups in the Rova-T arm (8.9 mo for patients with LDH ≤ULN and 8.5 mo for patients with limited disease), although these differences were not statistically significant. Within the Rova-T arm and within the topotecan arm, the median OS was numerically longer in patients with LDH less than or equal to ULN (versus those with LDH >ULN), in patients with limited disease (versus those with extensive disease on the basis of the Veterans Administration Lung Study Group stage at initial diagnosis), and in patients sensitive to first-line platinum-based chemotherapy (versus those resistant or refractory to first-line platinum-based therapy). Within the Rova-T arm, the median OS was substantially longer in patients with a previous history of brain metastases versus those without a history of brain metastases (Supplementary Table 1).
The median PFS (by investigator assessment) in the randomized population was also reduced in the Rova-T arm (3.0 mo [95% CI: 2.9–3.6]) versus the topotecan arm (4.3 mo [95% CI: 3.8–5.4]; HR = 1.51 [95% CI: 1.22–1.87]) (Fig. 2B). Among randomized patients with measurable disease at baseline (n = 416), the ORR was 15% (42 of 287) in the Rova-T arm, and 21% (27 of 129) in the topotecan arm (Table 2). One CR was observed in the Rova-T arm and none in the topotecan arm. A total of 41 (14%) had PR in the Rova-T arm compared with 27 patients (21%) in the topotecan arm. The median DOR was 3.5 months (95% CI: 2.8–4.2) and 4.9 months (95% CI: 3.9–7.9) in the Rova-T and topotecan arms, respectively. The CBR was 36% (103 of 287) with Rova-T and 43% (56 of 129) with topotecan (Table 2).
Table 2Efficacy Outcomes for Patients With Measurable Disease at Baseline
Objective response,
Per investigator assessment on the basis of RECIST version 1.1.
Complete response 1 (0.3) 0 (0)
Partial response 41 (14) 27 (21)
Stable disease 61 (21) 29 (22)
Progressive disease 154 (54) 58 (45)
Not assessable or incomplete data 30 (10) 15 (12)
Objective response rate,
n (%) 42/287 (15) 27/129 (21)
Clinical benefit rate,
n (%) 103/287 (36) 56/129 (43)
Median duration of response (95% CI),
mo 3.5 (2.8, 4.2) 4.9 (3.9, 7.9)
CI, confidence interval; RECIST, Response Evaluation Criteria in Solid Tumors; Rova-T, rovalpituzumab tesirine.
a Per investigator assessment on the basis of RECIST version 1.1.
Global health and physical functioning per the mean EORTC QLQ-C15-PAL scores were not appreciably different between the Rova-T and topotecan arms at baseline and after 6 weeks of treatment (Table 3). At week 7, the mean difference in scores between the Rova-T and topotecan arms was −3.53 (range: −8.23 to 1.16) for global health and −0.50 (range: −5.66 to 4.65) for physical functioning. However, at the final visit (the last valid postbaseline record of a patient), the mean difference in scores between the arms of –7.17 (95% CI: −11.39 to −2.94) for global health and −6.45 (95% CI: −11.73 to −1.18) for physical functioning suggested a further decline in global health and physical functioning in the Rova-T arm over time (Table 3).
Table 3Patient-Reported Outcomes Using the QLQ-C15-PAL and the EQ-5D-5L VAS Questionnaires
QoL Scale
LS Mean of Difference Between Groups (95% CI)
Calculated relative to the topotecan arm.
Visit Mean (SD)
LS Mean Change From Baseline (95% CI)
EORTC QLQ-C15-PAL
Scores range from 0 to 100, with higher scores indicating a higher level of functioning.
Baseline 255 64.84 (20.52) NA 117 65.38 (21.46) NA NA
Wk 7 217 61.37 (21.95) −5.86 (−9.19 to −2.54) 93 62.90 (21.72) −2.33 (−6.70 to −2.04) −3.53 (−8.23 to 1.16)
Final visit 255 52.71 (21.50) −13.29 (−16.36 to −10.22) 117 59.90 (22.64) −6.12 (−10.09 to −2.16) −7.17 (−11.39 to −2.94)
Physical functioning
Wk 7 217 66.4 1(23.80) −7.66 (−11.31 to −4.01) 93 66.38 (26.72) −7.16 (−11.95 to −2.36) −0.50 (−5.66 to 4.65)
EQ-5D-5L VAS
Scores range from 0 to 100, with higher scores indicating higher levels of self-perceived health.
Wk 7 212 68.45 (20.08) −3.65 (−6.57 to −0.73) 92 67.01 (20.03) −2.2 (-6.10, 1.55) −1.37 (−5.49 to 2.75)
Final visit 247 59.32 (20.50) −11.28 (−14.11 to −8.46) 116 65.34 (21.11) −4.23 (−7.86 to −0.61) −7.05 (−10.93 to −3.16)
CI, confidence interval; EORTC QLQ-C15-PAL, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care; EQ-5D-5L, five-level EQ-5D; LS, least square; NA, not applicable; QoL, quality of life; Rova-T, rovalpituzumab tesirine; VAS, visual analog scale.
a Calculated relative to the topotecan arm.
b Scores range from 0 to 100, with higher scores indicating a higher level of functioning.
c Scores range from 0 to 100, with higher scores indicating higher levels of self-perceived health.
Patients who received at least one dose of Rova-T (n = 287) or topotecan (n = 129) were included in safety analyses. A total of 273 patients (95%) experienced a TEAE in the Rova-T arm, and 125 patients (97%) experienced a TEAE in the topotecan arm (Table 4). The most common TEAEs (≥20%) with Rova-T were pleural effusion (29%), decreased appetite (25%), dyspnea (25%), fatigue (25%), nausea (23%), and pericardial effusion (20%). In the topotecan arm, anemia (61%), neutropenia (43%), thrombocytopenia (43%), nausea (31%), decreased appetite (28%), fatigue (27%), constipation (22%), and leukopenia (20%) were most common. Grade 3 or higher AEs were observed in 183 patients (64%) in the Rova-T arm and 113 patients (88%) in the topotecan arm and were primarily hematologic AEs in both arms (Table 4). Serious TEAEs occurred in 160 patients (56%) in the Rova-T arm and in 74 patients (57%) in the topotecan arm. The most common serious TEAEs included malignant neoplasm progression (10%), pneumonia (7%), pleural effusion (6%), and dyspnea (6%) in the Rova-T arm, and malignant neoplasm progression (13%), febrile neutropenia (9%), and thrombocytopenia (8%) in the topotecan arm (Supplementary Table 2). A total of 17% of patients (50 of 287) in the Rova-T arm and 30% (39 of 129) in the topotecan arm had drug-related serious AEs.
Table 4TEAEs by Severity Reported in at Least 10% of Either Treatment Group
TEAE, n (%)
Any-Grade
Any TEAE 90 (31) 119 (42) 64 (22) 273 (95) 12 (9) 85 (66) 28 (22) 125 (97)
Pleural effusion 70 (24) 12 (4) 0 82 (29) 5 (4) 0 0 5 (4)
Decreased appetite 64 (22) 9 (3) 0 73 (25) 31 (24) 5 (4) 0 36 (28)
Dyspnea 50 (17) 21(7) 1 (0.3) 72 (25) 24 (19) 1 (1) 0 25 (19)
Fatigue 56 (20) 15 (5) 0 71 (25) 27 (21) 8 (6) 0 35 (27)
Nausea 64 (22) 3 (1) 0 67 (23) 40 (31) 0 0 40 (31)
Pericardial effusion 53 (19) 4 (1) 0 57 (20) 3 (2) 0 0 3 (2)
Peripheral edema 50 (17) 2 (1) 0 52 (18) 11 (9) 0 0 11 (9)
Anemia 27 (9) 19 (7) 0 46 (16) 34 (26) 45 (35) 0 79 (61)
Photosensitivity reaction 41 (14) 5 (2) 0 46 (16) 0 0 0 0
Thrombocytopenia 17 (6) 27 (9) 0 44 (15) 19 (15) 36 (28) 0 55 (43)
Cough 41 (14) 1 (0.3) 0 42 (15) 16 (12) 0 0 16 (12)
Asthenia 34 (12) 3 (1) 1 (0.3) 38 (13) 18 (14) 3 (2) 0 21 (16)
Constipation 33 (12) 4 (1) 0 37 (13) 29 (23) 0 0 29 (23)
Malignant neoplasm progression 5 (2) 5 (2) 26 (9) 36 (13) 0 1 (1) 17 (13) 18 (14)
Pneumonia 13 (5) 12 (4) 7 (2) 32 (11) 5 (4) 6 (5) 0 11 (9)
omiting 28 (10) 3 (1) 0 31 (11) 17 (13) 1 (1) 0 18 (14)
Back pain 20 (7) 2 (1) 0 22 (8) 10 (8) 3 (2) 0 13 (10)
Diarrhea 21 (7) 1 (0.3) 0 22 (8) 25 (19) 0 — 25 (19)
Headache 20 (7) 1 (0.3) 0 21 (7) 9 (7) 4 (3) 0 13 (10)
Hypokalemia 11 (4) 7 (2) 0 18 (6) 10 (8) 4 (3) 0 14 (11)
Neutropenia 5 (2) 9 (3) 0 14 (5) 7 (5) 49 (38) 0 56 (43)
Epistaxis 9 (3) 0 0 9 (3) 11 (9) 3 (2) 0 14 (11)
Febrile neutropenia 0 4 (1) 0 4 (1) 1 (1) 13 (10) 1 (1) 15 (12)
Leukopenia 0 4 (1) 0 4 (1) 4 (3) 22 (17) 0 26 (20)
Alopecia 3 (1) 0 0 3 (1) 20 (16) 0 0 20 (16)
Rova-T, rovalpituzumab tesirine; TEAE, treatment-emergent adverse event.
The AEs of special interest (AESI), such as cutaneous reaction (39% versus 12%), edema (30% versus 10%), pleural effusion (29% versus 4%), pericardial effusion (20% versus 2%), and photosensitivity reaction (16% versus 0%), were more common in the Rova-T arm than in the topotecan arm. Hematologic AESI of thrombocytopenia (19% versus 48%), anemia (16% versus 62%), neutropenia (10% versus 62%), and febrile neutropenia (1% versus 12%) were less common in the Rova-T arm than in the topotecan arm. A complete summary of AESI is provided in Supplementary Table 3.
TEAEs led to death in 64 patients (22%) in the Rova-T arm and 28 patients (22%) in the topotecan arm. The most common AEs leading to death in the Rova-T arm were malignant neoplasm progression (n = 26; 9%), pneumonia (n = 7; 2%), and general physical health deterioration (n = 6; 2%), and those in the topotecan arm were malignant neoplasm progression (n = 17; 13%) and general physical health deterioration (n = 3; 2%). Five patients in the Rova-T arm had drug-related AEs leading to death, which included pneumonia (n = 2), pancreatitis (n = 1), atypical pneumonia (n = 1), and interstitial lung disease (n = 1). No deaths due to drug-related AEs were reported in the topotecan arm.
Rova-T targets a novel SCLC biomarker, DLL3. The TAHOE study enrolled patients with pretreated SCLC with high expression of DLL3, with the intent to select patients most likely to benefit from Rova-T. However, a shorter OS was observed in the Rova-T arm compared with the topotecan arm. The same trend of shorter OS in the Rova-T versus topotecan arm was observed in subsets defined by stratification factors such as platinum-sensitive versus refractory or resistant disease at baseline, the presence or absence of CNS metastases at baseline, a previous PCI (permitted only in patients without a history of brain metastases), and extensive versus limited disease at initial diagnosis. Notably, median OS was numerically longer within the Rova-T and topotecan arms for patients with favorable prognostic stratification factors, such as LDH less than or equal to ULN (versus LDH > ULN), limited disease (versus extensive disease), and platinumsensitivity (versus platinum resistance or refractoriness). Most patients had extensive disease at diagnosis, which could explain the high number of patients with brain metastases at baseline.
In the overall population, PFS was shorter and ORR was lower with Rova-T versus topotecan. Similarly, DOR was also shorter in the Rova-T arm compared with the topotecan arm. The MERU study, another phase 3 trial evaluating Rova-T as first-line maintenance therapy for advanced SCLC, although exhibiting longer PFS in the Rova-T arm versus the placebo arm, found no OS benefit at a preplanned interim analysis. The MERU trial was closed in August 2019. As a result, the development of Rova-T was discontinued on the basis of results from the TAHOE and MERU studies.
AbbVie discontinues Rovalpituzumab Tesirina (Rova-T) research and development program.
https://news.abbvie.com/news/press-releases/abbvie-discontinues-rovalpituzumab-tesirine-rova-t-research-and-development-program.htm
Date accessed: October 23, 2020
Phase 3 trial of Rova-T as second-line therapy for advanced small cell lung cancer (TAHOE study) halted.
https://news.abbvie.com/news/phase-3-trial-rova-t-as-second-line-therapy-for-advanced-small-cell-lung-cancer-tahoe-study-halted.htm
The present results from TAHOE are similar to a subset analysis of 238 DLL3-high patients in the TRINITY study, which evaluated Rova-T (0.3 mg/kg every 6 wk for two cycles) as a third-line or later therapy in SCLC—the ORR was 14.3%, the median PFS was 3.8 months, and the median OS was 5.7 months.
However, the current efficacy results are inferior to those observed in the initial phase 1 study evaluating Rova-T in patients with recurrent ES-SCLC, which exhibited an investigator-assessed ORR of 38% at active doses of 0.2 mg/kg or 0.4 mg/kg every 3 weeks or 0.3 mg/kg or 0.4 mg/kg every 6 weeks, with a median PFS of 4.3 months and also a DOR of 4.3 months in DLL3-high patients.
It should be noted that the analysis of the DLL3-high patients in the phase 1 study was exploratory and retrospective, the overall sample size and the size of the DLL3-high patient subset were small, not all enrolled patients had assessable tissue, and a different IHC assay was used to quantify DLL3 expression. All these factors may have contributed to the reported higher response rate in the DLL3-high subset of the early phase 1 study. In addition, the Rova-T dose in the TAHOE study was selected on the basis of a maximum tolerated dose and recommended phase 2 dose established in the phase 1 study.
The dose-limiting toxic effects at higher doses of Rova-T (0.8 mg/kg every 3 wk) observed in the phase 1 study limited the longer duration of treatment or higher dosing in the TAHOE study.
The analysis of quality of life using the EORTC QLQ-C15-PAL and EQ-5D-5L VAS scores indicated a higher decline in global health and physical functioning over time in the Rova-T arm compared with the topotecan arm. The safety profile of Rova-T in the TAHOE study was similar to that reported in other clinical studies.
Pleural effusions, pericardial effusions, edema, cutaneous reactions, photosensitivity reaction, and thrombocytopenia were AESI in the Rova-T arm. It has been postulated that the unique toxicity profile of Rova-T is because of the premature lysis of the linker, causing a systemic release of cytotoxic PBD.
Teicher B.A.
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Alternatively, a free drug may have a "bystander effect" on surrounding cells through diffusion out of the target cells or cleavage before internalization by cathepsin B, which is released by tumor cells or tumor-associated macrophages.
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An overall deterioration in the quality of life over time along with the unique toxicity profile associated with Rova-T, such as serosal effusions, suggest challenges for the tolerability of Rova-T treatment and warrant careful consideration of its potential toxicity in the fragile ES-SCLC population. In addition, topotecan exhibited a superior median OS (8.6 mo versus 6.3 mo) and CBR (43% versus 36%) compared with Rova-T, which supports the continued use of topotecan in the second-line ES-SCLC setting.
Although Rova-T did not improve the standard of care in second-line treatment of SCLC, it proved feasible in this study to select patients on the basis of tissue expression of DLL3 in the attempt to improve the therapeutic index of this approach. Other DLL3-targeting agents are being evaluated in this setting. AMG 757, a bispecific T-cell engager antibody against DLL3 and CD3, and AMG 119, an adoptive cellular therapy designed to target DLL3-expressing cells, are both under evaluation in phase 1 studies in patients with SCLC.
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Phase 1 study of AMG 757, a half-life extended bispecific T cell engager (BiTE) antibody construct targeting DLL3, in patients with small cell lung cancer (SCLC).
DLL3 is also typically expressed in castration-resistant neuroendocrine prostate cancer,
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gastrointestinal neuroendocrine carcinomas,
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and small cell bladder cancer,
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Clin Cancer Res. 2019; 25: 210-221
and thus, may be a useful target in a number of cancers.
Despite recent approvals of PD-L1 and programmed cell death protein-1 inhibitors in the first-
and third-line settings,
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no treatment has substantially improved OS in ES-SCLC since the 1970s.
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The TAHOE study joins several setbacks in second-line therapy, including the recent phase 3 CheckMate-331 study, in which the programmed cell death protein-1 inhibitor nivolumab failed to improve OS versus topotecan or amrubicin.
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Albeit disappointing, improvements in the understanding of SCLC gained in these trials may contribute to eventual breakthroughs in the treatment of SCLC.
This study was funded by AbbVie, Inc., which also participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. The authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Swati Ghatpande, PhD and Allison Cherry, PhD of Bio Connections, and funded by AbbVie, Inc. Dr. Blackhall contributed to the study conceptualization and resources and the writing of the manuscript. Dr. Jao contributed to the writing and review of the manuscript. Drs. Greillier and Erman contributed to the study investigation and resources, and the writing and review of the manuscript. Dr. Nackaerts contributed to the study visualization and resources and the writing and review of the manuscript. Dr. Sun contributed to the formal analysis, data curation, and writing and review of the manuscript. Drs. Luo and Komarnitsky contributed to the study supervision and the writing and review of the manuscript. Ms. Tanwani and Caffrey contributed to the study resources, data curation, and review of the manuscript. The remaining authors contributed to the study resources and the writing and review of the manuscript. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. Rovalpituzumab tesirine (Rova-T) has been developed by AbbVie, Inc. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), and other information (e.g., protocols and clinical study reports) as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided after review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.h.
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Supplementary Tables 1-3
(Accessed January 10, 2020)
Accepted: February 9, 2021
Received in revised form: January 29, 2021
Received: December 18, 2020
Disclosures: Dr. Blackhall reports participating on advisory boards of AbbVie, AstraZeneca, Roche, Boehringer Ingelheim, Novartis, Pfizer, Celgene, Regeneron, and Amgen. Dr. Jao reports serving on the advisory boards of AbbVie, Roche, AstraZeneca, and Merck. Dr. Greillier reports participating on the advisory boards of AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. Dr. Cho reports receiving research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp.; serves as a consultant for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, and Blueprint Medicines; has stock ownership at TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, KANAPH Therapeutic Inc., Cyrus therapeutics, and Interpark Bio Convergence Corp.; serves on the scientific advisory boards of KANAPH Therapeutics Inc., Brigebio Therapeutics, Cyrus Therapeutics, and Guardant Health; serves as a member of the board of directors of Gencurix Inc. and Interpark Bio Convergence Corp; received royalty from Champions Oncology; and is the founder of DAAN Biotherapeutics. Dr. Penkov reports receiving honoraria from AbbVie, AstraZeneca, GlaxoSmithKline, H3B, Janssen, Merck Sharp & Dohme, Mylan, Nektar, Pfizer, Polyphor, Prestige, Regeneron, Roche, Takeda, and Tanvex. Dr. Reguart reports receiving research grants from Pfizer and Novartis; and served in the consulting, advisory, and speaker activities for Merck, Roche, AstraZeneca, Pfizer, Amgen, Novartis, Eli Lilly, Takeda, and Boehringer Ingelheim. Dr. Majem reports receiving grants and personal fees from Bristol-Myers Squibb; personal fees and nonfinancial support from Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, and Roche; personal fees from Kyowa Kyrin; and personal fees from Pierre Fabre and Novartis outside the submitted work. Dr. Nackaerts reports participating in advisory boards for AbbVie, Boehringer Ingelheim, Novartis, Pfizer, and Roche. Dr. Schuette reports receiving sponsorship from and served a consulting or advisory role with Roche, Eli Lilly, Amgen, and Merck. Dr. Cappuzzo reports serving in an advisory role for and received honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Bayer, Pfizer, Roche, Pharmamar, and Takeda. Dr. Okamoto reports receiving grants from AbbVie, Astellas Pharma, and Boehringer Ingelheim during the conduct of the study; and grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Eli Lilly Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Merck Sharp & Dohme Oncology, and Novartis; and personal fees from Pfizer outside the submitted work. Dr. Erman reports receiving honoraria and consulting fees from Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, and Nobel. Dr. Langer reports receiving a research grant from AbbVie, and participated in the advisory boards of Merck, Roche, AstraZeneca, and Pfizer. Dr. Kato reports receiving grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck Biopharma, Merck Sharp & Dohme, Novartis, Ono, Pfizer, and Taiho; received personal fees from Boehringer Ingelheim, Daiichi-Sankyo, F. Hoffman–La Roche, Nippon Kayaku, Nitto Denko, Shionogi, Sumitomo Dainippon, and Takeda; and grants from Astellas, Kyorin, Kyowa-Kirin, and Regeneron outside the submitted work. Dr. Groen reports to have participated on advisory boards of AbbVie. Dr. Reinmuth reports receiving honoraria for speaker activities and participation in advisory boards for AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, and Takeda. Dr. Sun, Dr. Luo, Ms. Tanwani, Ms. Caffrey, and Dr. Komarnitsky are employees of AbbVie and hold AbbVie stock. The remaining authors declare no conflict of interest.
DOI: https://doi.org/10.1016/j.jtho.2021.02.009
© 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Linked Article
All That Glitters Is Not Gold: The Story of Rovalpituzumab Tesirine in SCLC
Journal of Thoracic OncologyVol. 16Issue 9
Extensive-disease SCLC (ED-SCLC) is a recalcitrant disease. There had been no new therapies for more than three decades and no improvement in patient outcomes until the introduction of immune checkpoint inhibitors (ICIs) in the first-line setting. These agents, atezolizumab and durvalumab, have modestly improved the survival of the patients with ED-SCLC.1,2 For a previously treated population, topotecan, amrubicin (approved in Japan), and recently lurbinectedin (only approved by the Food and Drug Administration [FDA]) remain the only approved treatments.


( January 17, 2015, Colombo, Sri Lanka Guardian) Following a meeting of the Sri Lanka Freedom Party (SLFP) held yesterday, President Maithripala Sirisena who assumed the chairmanship of the Party is to review its Constitution to enable former President Chandrika Bandaranaike Kumaranatunga to be the SLFP's future leader.
Currently according to the SLFP Constitution, the serving head of State has to assume leadership of the Party, in this case Maithripala Sirisena.
However according to a resolution by the JHU's Ven. Athureliya Rathana Thera and his Pivithuru Hetak organization, the President of the country does not have to be the head of the SLFP wherein even a member can hold the post.
It was also the same agreement reached between Chandrika and UNP leader Ranil Wickremasinghe when Maithripala Sirisena was nominated as Common Opposition candidate.


You might remember Godzilla demolishing San Francisco's Golden Gate Bridge, or Matthew Broderick defeating the monster in New York, but what do you know about Godzilla's nuclear past?
The original Godzilla film tackles the threat of the atomic age and nuclear weapons, it's about Japan being drawn into war again, and about people living with the constant threat of bombs and destruction. Godzilla, or Gojira, was one of the first films to show the full extent of the devastation that Japanese civilians experienced when the United States dropped bombs on Hiroshima and Nagasaki at the end of World War II.
30 Godzilla films have been produced since Ishirō Honda's 1954 Japanese science-fiction original. In that time, the monster's story has morphed from a nuclear allegory into a Hollywood cliché – but recent events show that our fear of nuclear catastrophes is far from over. Wikipedia searches for 'Godzilla' spiked following the 2011 Fukushima Daiichi nuclear disaster, showing that the monster's power as a window into post-war attitudes about the dangers of nuclear radiation still rings true today.
Dr Jason Christopher Jones of Monash's Japanese Studies program has been interested in Japan since he was a child. His inspiration? Video games. In his youth, everything was text based, and in order to know what was happening in the game, he had to learn to read it in Japanese. Dr Jones recently spoke to us about how the Godzilla films reflect Japan's experience of nuclear tragedies, just one of his particular areas of research.
Jason joined Monash University in 2015. He is a lecturer in Japanese Studies in the School of Languages, Literatures, Cultures and Linguistics, and researches wine manga, Godzilla and themes of cultural exchange and adaptation. In addition to his research, he is an active translator and interpreter.


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Par Comm unhappy over govt silence
Edited By Odishatv Bureau Published By Odishatv Bureau On Jun 2, 2011 - 1:39 PM
New Delhi: A Parliamentary Standing Committee has expressed its unhappiness over Centre`s silence on opening bigger hospitals in Naxal-affected areas, saying lack of health care leads to dissatisfaction among the people.
The department-related Parliamentary standing committee on Home Affairs in its report said special packages are required to be formulated for providing health care for people in Maoist-affected areas, both under the existing schemes as well as new schemes.
New primary health centres and sub-centres need to be opened and it should be made compulsory for the new doctors to serve in those areas by giving some incentives to them.
The Committee, headed by BJP leader M Venkaiah Naidu, also said, in some selected places, bigger hospitals are also required to be opened with all the facilities, including major specialities. Special efforts are needed to be made for health care of women and children.
The report was submitted to Rajya Sabha Chairman Hamid Ansari today.
"The Committee is unhappy to note that the government has not indicated anything relating to opening of bigger hospitals in some selected places of Left Wing Extremism (LWE) areas.
The government may give special consideration for this," it said.
"Lack of health care in Naxal-affected areas is another basic issues that leads to dissatisfaction among the people," it noted.
The government, in its action taken report, said that it has identified 34 LWE affected districts in eight states for focused attention and to address the issue of lack of health care, many interventions have been initiated under the National Rural Health Mission.
The Committee also expressed concern over the incidents of jail break and attack on police by the Naxals and termed it as "direct challenge" to the authority of the state.


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Home > Transfer News > Arsenal Hoping To Secure Deal For Egyptian Playmaker – Reports
Arsenal Hoping To Secure Deal For Egyptian Playmaker – Reports
By mac14 on July 1, 2015
According to the Metro, Arsenal are hoping to see-off competition from AS Roma to secure a deal for highly-rated Egyptian playmaker Ramadan Sobhy.
We have a long-standing interest in the 17-year-old and reportedly invited the youngster for a trial at London Colney back in February but his club Al Ahly refused our approach as they believe he's too good to have to undergo a trial [much like Zlatan Ibrahimovic].
However, it appears we've now renewed our interest as the Metro claim that Arsenal are looking to wrap-up a deal for the young attacker over the coming weeks.
We'll face stiff competition from Roma – who are also showing a keen interest – but the newspaper suggests that Arsene Wenger is hopeful of beating the Italian outfit to Sobhy's signature this summer.
We'll have to wait and see if that turns out to be the case but Sobhy is certainly a big talent who has the potential to go on to have a fine career at the highest level.
The teenager has scored 7 goals in 22 matches for Al Ahly and has been dubbed as the 'best youngster in Africa' by some corners of the media.
He's predominantly a left-sided attacker but is capable of playing anywhere across the front three positions. However, if we do end up signing him I'm sure Arsene and his scouts will assess his abilities before deciding on a final position.
ArsenalArsene Wengertransfer news


Rainy days, frosty temperatures and scorching scorching days are all legitimate factors to spend the day indoors. Just because you are caught indoors, nevertheless, doesn't mean that you can't have some great family members enjoyable. There are numerous indoor activities to keep your family members busy, meanwhile, investing time together and bonding with one an additional.
"Families will want to stay through a number of live shows by the Mad Researchers, as every display is various from the prior one," Schulman explained of the team's performance at final yr's Evening at the Museum.
Home Science Home Experiments are great for rainy or dreary days when the children are restless and looking for something to do. If you consider a appear around, you will see that you have a great deal of things that can be utilized to experiment with. For instance, you could have your kids test various issues to drop eggs on to, this kind of as a couch, a bed, a carpet, a stuffed animal to see which will take the egg without it breaking. Sadly this experiment can often result in a mess!
Super Why: My son enjoys the superhero aspect of this show, and I adore the way he can lookup for letters along with "Alpha-Pig" and help the characters solve the issues.
Field Working day – As soon as in a whilst, get out with your children and have a stroll. There's science all around you. Go to the zoo and educate them concerning wildlife. Go to the woodland and educate them about plant life. Visit the shopping mall and teach them about the most sophisticated technologies. Go to the food marketplace and educate them why some food products are usually good or bad for the well being.
Science fair projects need to be tickle the creativeness of the student. The venture can be fairly easy but the idea requirements to challenge the intellect. If mothers and fathers are performing a lookup on the web, they need to know that they will most likely end up totally irritated. Numerous websites will give part of an experiment and make you pay for the relaxation. Or, some websites will make you subscribe, paid of program, to the website to see the selection of experiments. Numerous of the websites will merely immediate you to unrelated web sites.
Every working day is different in the life of homeschoolers. Every day is an opportunity for a new adventure! Every opportunity is a new studying encounter! Every working day reminds me how blessed we are to be studying at house, together! And, every working day, I am thankful that I reside in a country that enables me the freedom to choose the academic method I want my kids to have!