Now there’s a wedding in Bear Creek and Elizabeth is determined to make her daughter proud of her by being engaged in the pre-wedding craziness, creating a beautiful garden for Suzie and Kit to marry in and open herself up to friendships offered by Suzie’s circle of friends. We first met Elizabeth back in Doctor Daddy Bear when her daughter, Suzie met her mate, Kit. That may sound like any Mother of the Bride activities but Elizabeth is a very quiet, shy woman who in so Reviewed at Shifter Haven Reviewed at Shifter Haven We first met Elizabeth back in Doctor Daddy Bear when her daughter, Suzie met her mate, Kit. I have loved the Bear Creek Clan stories, the Karal series, Borderlands, too. You'll love returning to Bear Creek, the great folks, strong men and women, and cherished loved ones. New loves, weddings, melding families and fears falling away. Marvelous characters, a smooth flowing plot, and a simply lovely story. She is warming to the idea of sudden "love" in her life. ![]() Elizabeth's fears are mulled over, as the festivities move along. Elizabeth stuns him, she is it, and he wastes no time telling her. Dean is a foster Dad, has waited his whole life, 40 years, for his fated mate. Elizabeth, about 40, is shy and has a birthmark on her cheek, and always fears people's reactions. Marvelous characters, a smooth fl *** This is an especially sweet tale as we return to Bear Creek for Elizabeth's daughter's wedding. *** This is an especially sweet tale as we return to Bear Creek for Elizabeth's daughter's wedding. Elizabeth needs to find the strength to overcome her fears and be there for her daughter.Īn encounter with a bear shifter, who tells her she is his mate, helps change her world, opening up new possibilities she’d never dared dream would be hers.Ĭan she grab hold of her dreams, and not let go? Despite her fears, can she open her heart to a man who promises to love her forever?. But now the one person in her life she truly loves, her daughter Suzie, is getting married. She has always struggled to meet new people and visit new places. His life will never be the same again.Ī birthmark on her face has haunted Elizabeth her whole life. Then she walks into his life, the most beautiful woman he’s ever seen. Instead, he’s carved out a fulfilling role as a foster parent to older kids. She has always struggled to meet new people and visit ne Bear shifter, Dean, has almost given up on finding a mate. ![]() A birthmark on her face has haunted Elizabeth her whole life. Bear shifter, Dean, has almost given up on finding a mate.
0 Comments
![]() The program is distributed free of charge. The contents of the download are original and were not modified in any way. The download version of SciTE - Scintilla Text Editor with Extensions is 2.01. Het maakt gebruik van de opensource-Scintilla Text Editor-bibliotheek, die van. Scintilla Text Editor is een opensource- en cross-platform teksteditor. SciTE is a free SCIntilla based text editor useful for general text editing, but specifically geared towards programming. news reviews top programs Windows Mac Web Apps Android En Deutsch Espanol. Fast downloads of the latest free software! Click now. A Beginner#x27 s Guide to Install gcc and g Compiler on Windows 10.ĭownload NetBeans IDE 8.0.1 for Windows. THE DEFAULT DOWNLOAD LOCATION IN WINDOWS 11 // 10!. ![]() PS: On Windows 10 圆4 64-Bit is also the 32-bit Program-Folder: shell:programfilesx86 Use shell:programs for the Start-Menu folder in Windows-10! The address shell:Common Programs is for all User Programs in the Windows 11 / 10 Start-Menu folder! 2. SciTE4AutoHotkey is a lightweight and easy to use SciTE-based AutoHotkey script editor. Scite Jump - CNET Download.ĭownload: Download SciTE4AutoHotkey 3.0.6.1. ![]() If not, double-click the directory quot wscitequot. Highlight and copy all the files you see. SciTE Click here to Download Scintilla#x27 s SciTE file authorize the download if blocked. On the Windows desktop, click quot Start / runquot, enter quot cmdquot then, in the DOS window enter quot cd c:#92 mingw#92 binquot then enter. It may be used for any purpose, including commercial purposes, at absolutely no cost. Lua is free software distributed in source code. Download source binaries previews logos tools test suites extras license versions donations live demo. Download NetBeans IDE 8.0.1 for Windows - F.ĭownload X-SciTE - Create applications in a powerful environment with support for an abundance of programming languages, syntax highlighter and more. Always available from the Softonic servers Free amp fast download Always available Tested virus-free Free Downloadfor PC. Download SciTE - free - latest version Windows Development amp IT Programming Languages SciTE Download Download SciTE for PC Free In English V 5.1.5 3.9 185 Security Status SciTE free download. Follow the on screen steps and it will be installed into the default location program. Extract the downloaded zip file using win zip/7z or any other utility. Steps to download Turbo C for Windows: Download Link: Turbo.C Download Turbo C zip file from the link above. Scite: A smart citation index that displays the context of citations. Features - Full MinGW and GTK SDKs Autocomplete.190 - Do system scripting bash, applescript, cmd, powershell, perl, j/vbscript, awk - Examine all sorts of data files sql, regedit, mib, xml, yaml, json, vcard. Refurbished SSciTE with some additional patches. GitHub - rjpcomputing/luaforwindows: Lua for Windows is a #x27 batteries.ĭownload myScite for free. Step 2: Connect the device once the installation is done. Step 1: Download and install the program on the PC. So, if you are unable to find correct driver software, install the application first and try to connect the smartphone to the computer using a recommended USB data cable. ![]() Text editing in SciTE works along the same lines as most Windows text editors, so using it should be relatively familiar to most. SciTE SCIntilla 5.2.2 Major Geeks Special Offer: -= advertisement =- SciTE is a SCIntilla based text editor designed to be a useful text editor and includes essential tools for building and running programs. SciTE is an open scorce text editor that can be both used as an. File Details: File Size: 2.1 MB: License: Freeware: Operating System: Linux, Windows 7/8/10/Vista/XP: Date Added: April 4, 2022: Total Downloads: 5,366: Publisher: Scintilla: Homepage: SciTE: Publisher#x27 s Description. tags: 圆4 Office 2016, 圆4 SharePoint Workspace, 圆4 Office, 圆4 Word, 圆4 Excel, 圆4 Document Editor, office 365 圆4, 圆4 PowerPoint Presentation. Powerful new tools to express your ideas and connect with people. Top Office Suites amp Tools 64-bit downloads. Create, edit, and share your professional looking videos. Scrnli Screenshot amp Screen Video Recorder. Scite allows users to see how a publication has been cited, providing the citation context and classification. Windows Spy Keylogger Tool 2021 - SecurityXploded.Windows 3 0 Vista download - Scite Vista download - Best Free.A Beginner#x27 s Guide to Install gcc and g Compiler on Windows 10.Download NetBeans IDE 8.0.1 for Windows - F.Scite: A smart citation index that displays the context of citations.GitHub - rjpcomputing/luaforwindows: Lua for Windows is a #x27 batteries. ![]() I keep my phone on silent at night (the time when most people on the planet would want it to be on silent) and in the first night using this app it worked fine. I downloaded this because I have a hard time finding an alarm with a customizable snooze. There are a ton of glitches as well, like it will say the next time it’s set to go off is Thursday, but it’s programmed for Tuesday. Everything is was set up for it to go off and it didn’t. If your device supports a battery saving function, please add myAlarm to the whitelist to prevent malfunction with the alarms. Your phone must be TURNED ON for the alarm to work. MyAlarm Clock is the perfect alarm clock app for those who want a different wake up experience every day, it's very easy to use, customizable, for a gentle wake up in the morning or for heavy sleepers. Use the built-in flashlight to avoid groping around in the dark. Set timer to fall asleep listening to a relaxing music or a smooth radio station. You can dismiss the alarm by touch, shake, double tap or math calculation (perfect for heavy sleepers). Prevent excessive snoozing by selecting snooze time and number of snoozes. You can even set another type of alarm after the alarm stops.Ĭhoose a relaxing music or set a quiet alarm clock to smoothly increase volume to wake you up gently in the morning (adjust the sound volume to fit your needs). Restrict alarms only at your location or Wi-Fi you're using. Use vibration, alarm with flash or light show. Set your favorite track as a music alarm and wake up listening to music.Ĭhoose between different themes/colors and many digital or analog clocks. Up to 100 radio stations per country available. ![]() Wake up with your favorite radio station or podcast (choose country in settings). Set as many alarms as you like, recurring or one-time alarms, for specific days of the week or holidays. You can simply choose a ringtone, relax music or (with our talking alarm clock) wake up with real time weather information and headline news. Sleep better, wake up easier and be always on time! MyAlarm has a lot of features that allow you to customize your wake up experience. ![]() ^ a b "Up Your Alley Billboard Singles"."Joan Jett / Joan Jett & the Blackhearts - Up Yor Alley". Bob Ludwig – mastering at Masterdisk, New York. ![]()
![]() Dirty horny woman let dog fucking hard POV. Big tits blonde woman loves dog sex hard. Horny Woman Loves Getting Her Ass Fucked Hard. Dog get fuck hard Old woman - Amateur free porn - Fapdig. 8:51 Zoo sex tube with a collared hottie in HD 0:56 Beautiful farm bestiality with my hubby 8:42 Animals. Pet Sex Videos Animal Zoo Sex Zoo Porn Zoofilia Porn XXX Zoo Porn Animal Sex Porn Tube. Dog Sex Animal Fucks Zoo Sex Zoo Porn Horse Sex Bestiality Sex Dick Zoofilia Blonde With Animal Pussy Cock Slut. 78% likes (2251 voices) Added 5 years ago. Dog with large penis shags woman in brutal amateur scenes. ![]() Indian teen having Romantic sex on the floor and gets creampied. 18yr indian teen school girl seduces and fucked very hard by desi hindi teacher in clear hindi talks. Explore tons of XXX movies with hot sex scenes ready to be watched right away. Woman tied up to get fucked by dog in bestiality bondage - ApornTV. Redhead enjoys hot sex with a brown animal here. Most Recent Girls and Dogs Videos - Animal Porn Rocks Beastiality Videos. Home Latest Top Rated Most Viewed Categories Channels [black girl fucked by dog [black girl fucked by horse drugged girl fucking animal dog fuck girl young girl fucks dog dog rape girl 2 dogs one girl young girl fucking. 60 FPS, Amateur Blowjob, Amature, Big Boobs, Creampie Pussy, Japanese Pussy, Japanese Sex, POV Blowjob, POV Sex, Runaway BadB0y 04:07:04. If you also like to watch how big cocks are pushed from behind into the narrow cracks of exciting mares, then the porn films from porngooo. Many sluts are on it when they are fucked from behind and are pulled properly by the hair. Submissive wife lays on her back and gets fucked by a huge. ![]() Best Dog with woman porn videos page 1 at. Horse fuck scene with a small boobed beauty. Hot and sexy girl being fucked by her boyfriend in the barn and other pet lover chick is fucking horse dick. Women fucked by dog - Extreme Porn Video - LuxureTV. She enjoys hardcore sex with the animal and her loving husband helps her out along the way. Perfect booty blonde gets fucked by a kinky doggo. Tags: beastiality XXX sex with dog dog rape his owner. He recently recorded this beastiality video where their dog pounds her good. Nice girl fucked by dog.ĭog rape woman! Before this milf married her husband she was somewhat reserved and shy, now she's a sex crazed slut that will do whatever he asks her to. Leggy young zoofil is tasting sperm of a stallion. Hot-shaped lady in high heels drilled by doggy. Interracial lesbians sucking fucking dog. Dog fuck women pussy from behind - Beastiality. Pig boar fuck girl Ariel - k9 lady HD porn - ZooTube Videos. ![]() Vidéos porno similaires à Girl fucked dog. De: Vidéos Porno XXX - Sex TuKif Porno Gratuites. Girl fucked dog La belle Blondie Danni se fait défoncer par le chien sale. Girl fucked dog - Vidéos Porno et Sex Video - Tukif Porno.Ĭhinese wife slut get fucked by dog - LuxureTV.Lady fucks a dog - XXX Videos | Free Porn Videos.Dog get fuck hard Old woman - Amateur free porn - Fapdig.Woman tied up to get fucked by dog in bestiality bondage - ApornTV.Submissive wife lays on her back and gets fucked by a huge.Best Dog with woman porn videos page 1 at.Dog fuck women pussy from behind - Beastiality.Chinese wife slut get fucked by dog - LuxureTV. Supports a wide range of Linux distributionsīeyond Compare supports a wide range of Linux distributions, including Red Hat Enterprise Linux, Ubuntu, Fedora, SUSE Linux Enterprise Server, openSUSE, Debian GNU/Linux, Mageia, Linux Mint, and any other DEB- or RPM-based operating system. It allows you to view and edit text files with syntax highlighting, using comparison rules that have been created specifically for documents, HTML and source code. It is an intelligent applicationīeyond Compare is an intelligent application that will automatically choose the best way to compare files and folders, displaying the results in the format you want. With Beyond Compare, you will be able to quickly compare entire drives, directories and folders, check modified times and file sizes, integrate zip archives and FTP sites seamlessly, as well as to use byte-by-byte comparisons. Features powerful commandsīeyond Compare features powerful commands that allow you to ignore the differences you’re not interesting in and focus only on the ones you really want to view, merge changes, generate reports, as well as to synchronize your files across multiple devices. It even supports folder comparison operations and can compare Adobe PDF (.pdf) and Microsoft Word (.doc) files. ![]() ![]() ![]() The software has been designed to allow users to easily and quickly compare any type of files, including text documents, images, MP3s, HEX data, or entire drives. Beyond Compare is a commercial, cross-platform and full featured graphical software that provides a file compare and directory synchronization utility for GNU/Linux, Microsoft Windows and Mac OS X operating systems. ![]() Mastermind Game: The Strategy Game of Code Maker vs. Winning teams then post their scores at the front of the room to determine the winner! 4. The more questions a group gets right, the more points they get. ![]() If the student drawing the card gets the correct answer, they are awarded a point! Next, one student at a time will take turns rolling the dice and answering the inquiry on the card drawn. Making a team name is all part of the fun. Students can draw on their existing knowledge to respond to whatever question they find themselves being challenged with.įirst, have each team get out a piece of paper and fill in each team’s name. How to Play in the Classroomīecause this game allows up to 8 players, the whole class can be divided into small or larger groups. The Professor Noggin game allows students and teachers to use content from class to reinforce learning. Why teach about history and art and be boring when there is a trivia game that makes the process a lot more fun? History and Art from around the world plays a part in modern-day culture everywhere. Professor Noggin’s History of Art Trivia Game This activity is a great way to use math skills. If working toward a larger state, kids must fill in the fraction for the state’s electoral votes. Students must roll the dice and decide to take states or work toward larger states: For example, if a student rolls a four with the dice, they can choose to work toward a state where the electoral college only has four points, one with a bigger point count. There are two versions of this game - addition and multiplication. Teachers and their students can participate together! Students may play this game with two teams or between two students!įirst, divide the class into two teams, or if you have several copies of the game, kids can be in a group of two. This math game is a fun game to play and a great way to get students interested in voting. No need to track down any pieces of paper because Election Night boards are dry erase friendly. Students will love the competitive nature of this game in the process of learning different strategies, math, geography, and civics. Many kids will go through school without having a good understanding of how the electoral college works. What can be more important than learning how elections work in the United States? Election Night board game teaches children the process of the road to becoming the President. In the end, students can choose one story as the winner and make a game of it! 2. Another option is to have three different teams in the class, and each comes up with a different story, then a student from each team reads theirs to the class. What is more fun than storytime? Have one student at a time go around the classroom and share it with the rest of the class. Students can use these dice to come up with different stories on an individual basis or be used in small groups to create a collaborative story. Rory’s Story Cube Dice allows students to develop stories with twists and storylines creatively. Adding more dice along the way will certainly add to the fun! How to Play in the Classroom This bundle can be added to the dice sets and to the dice’s little pouch for storage. The set has six items: 9 original dice sets, 9 Action dice, and 9 Voyages dice. Rory’s story cubes are a wonderful addition to any classroom and for any age. Our Top 10 Classroom Games and Activities Reviewed 1. Practice Vocabulary Words – Vocabulary Jam.Team Building Games – EXIT: 3-Pack Escape Room Bundle.History and Art – Professor Noggin’s History of Art Trivia Card Game.Allow for games that involve small groups for students that may be uncomfortable playing in a large setting.ġ0 Best Classroom Games and Activities at a Glance.Pick a great game that will solidify skills that you have been working on with your students, i.e., vocabulary words or number concepts.Choose fun games you, the teacher, can participate in with your students.Some of the best games involve teamwork and the whole class.This can allow the kids to fill in something or ask their own questions. Choose a game that allows all students a chance to participate.You want to have games that capture the student’s attention while also having fun! When looking for a fun classroom game or review activity, you don’t just want something to pass the time. Here, we have researched the best classroom games available on Amazon and some free fun games! What educator doesn’t like using free resources, right? How to Choose the Best Classroom Game One thing that is bound to get the competitive learning nature of students going is a good-ole-fashioned game! “School is supposed to be boring,” said no teacher ever! Fun classroom games begin with a teacher who knows how to engage and motivate their students through other teaching methods. ![]() Hence, if it opens a cell, there is an 80% chance of the agent receiving the correct information. Unlike a typical mineweeper game where the agent will know what lies behind a cell once it is opened, this solver will only get the information with some probability. where the level number is a multiple of 5) has so many traps that you'll need to use some of your axes/dynamite/maps to get through unscathed. Bonus CSP Solver: This is just en extension of the the CSP solver. Four out of every five levels can be completed using logical deduction only to find the way through to the exit (you don't need to guess or use pick axes/dynamite/maps).To achieve this goal, you will be able to take knowledge of the number of mines in the. To win, you need to find the location of all mines. Initially, mines, buried, are obviously not visible. To do this, it has been split into squares that can contain either a single mine or none. When it opens a cell or flags it, the knowledge base is updated and the constraints/equations are resolved. How to play MineSweeper You must clear this minefield. It plays the game just like a normal human - by creating different constraints for each square opened and each mine flagged. ![]() CSP refers to Constraint Satisfaction Problem since this is the main algorithm used by the agent. CSP Solver: This is the main bot which plays the game just like humans.It is a baseline model which we developed to evaluate the accuracy and effectiveness of the other complex models. It will stop the game if there are no further safe moves possible. Basic Solver - The basic solver is the most risk-free solver which will not think on its own but just play the safest moves possible.As the name suggests, the project goal was to create a computer bot which can play Minesweeper at different difficulty levels. Minesweeper Genius is available now for Switch, PS4, and Xbox One.This was second project for CS520 - Introduction to Artificial Intelligence. Don’t have an account? Sign up here and join in on the Microsoft Windows fun! Make sure you comment using a Dtoid account with your current email address on file. The version of Minesweeper before your eyes (Minesweeper Pro) was designed for people who want to play the game in an Internet browser and who do not like the random. It appeared first in Windows 3.1 as a way to help users master the mouse right-click. Winners will be drawn on Friday, March 1. Minesweeper became popular due to its distribution with operating system Microsoft Windows. Our Switch and PS4 keys are for North American accounts, only. We have three keys each for Switch, Xbox One, and PS4 to give away. I’m looking forward to what you come up with. To enter to win your copy, give us a way to make a standard-issue Windows game as ridiculous as this one. Had I not learned to play Minesweeper that day, I wouldn’t have done this contest. Which leads me here, at this exact point in time, to this. My teacher wasn’t terribly happy with me when I finally got back to class, but I gained a new skill that day. Arcade levels are levels of non-standard shapes and sizes. I asked what she was doing, and she spent about 45 minutes showing me how to play Minesweeper. Classic levels are the usual levels of the classic Minesweeper: 9×9, 16×16 and 30×16, but in the design of the chosen theme. But the librarian was playing Minesweeper on the only computer in the school. My teacher sent me to the library to get some books for the class or something, I don’t really remember. Watch out! I really don’t know what else I can say about this, so I’ll tell you instead about when I first learned how to play Minesweeper. There’s a switch that moves your Aristotle clone around some, and then some other things get in the way. There are 130 regular levels, and 55 bonus challenge levels to go through. You go around a board and try to not hit mines. Which is why I’m giving away a bunch of copies of it. It makes so little sense that it makes perfect sense. Take Minesweeper Genius for instance - the whole premise is that aliens have cloned Aristotle, and in order to extract his genius they’re making him solve a bunch of Minesweeper puzzles. Feel like a friggin’ genius with today’s contest: Win a Switch, PS4, or Xbox One copy of Minesweeper Genius. Heroes & Generals … Resolution: 1920x1080 Heroes & Generals – #11 – Jak niszczyÄ czoÅgi? Resolution: 1920x1080 88u4mFz.jpg Resolution: 1920x1080 Heroes-and-Generals-wallpaper-2.jpg Resolution: 1920x1080 9550HandG_Action_Screenshot_GDC_03. With the bazooka or panzerschreck, the two launchers you can spawn with, you have three range … Resolution: 1920x1080 Heroes and Generals Gameplay Español Full HD Resolution: 1920x1080 Getting gold! Resolution: 1920x1080 Hero and general wallpaper Resolution: 1920x1080 Weapons 2560Ã≱440 Resolution: 2560x1440 Featured Images Resolution: 1920x1080 Game Overview. The update improves light tank … Resolution: 1920x1080 Boxart Resolution: 1920x1080 Heroes and Generals Live Commentary #1! (Heroes and Generals Gameplay) Resolution: 1920x1080 Free Gold to celebrate Victory Day Weekend Resolution: 2560x1440 Free Ribbon Booster gets your Heroes in shape! Resolution: 1920x1080 Night fighting Resolution: 1920x1080 To engage enemy armor with a rocket launcher is different. Heroes & Generals … Resolution: 1920x1080 … Heroes and generals screenshot … Resolution: 1920x1080 Developer Reto-Moto has announced a new update to their World War II MMOFPS Heroes & Generals called Zhukov – Armored Ambush. CompanyofHeroes2_E3_T34 Resolution: 1920x1080 Image result for nagual caro Resolution: 1920x1080 SU_Amoeba_Leaf_Camo_press Resolution: 1920x1080 … Heroes & Generals screenshot 31 … Resolution: 1920x1080 NewRenderComparison_VM.jpg Resolution: 1920x1080 Artwork 1920Ã≱080 Resolution: 1920x1080 … Heroes and generals screenshot Resolution: 1920x1080 Recent Squad Tweaks In Details! Resolution: 1920x1080 maxresdefault.jpg Resolution: 1920x1080 Heroes and Generals – NEVER TRUST JEEPS Resolution: 1920x1080 US Scopes Resolution: 1920x1080 Company Of Heroes 2 : HD Wallpapers | I Have A PC Resolution: 1920x1080 Amphibious Typ 166 Schwimmwagen Resolution: 1920x1080 11 July 2014 Resolution: 1920x1080 Guide updated with Bauer build. ![]() In addition, you can view below the wallpaper to full screen, just click on them with the left mouse button and wait for the download Company Of Heroes 2 Video Game.Heroes And Generals Tiger Tank Attack Hd Wallpaper Resolution: 1920x1080 The content of this article is more than three months old and may not be relevant to the current version of the game Resolution: 1920x1080 CompanyofHeroes2_E3_Church. The downloaded archive will be presented to all the images that are here in a convenient and high-quality format. And, you can always download all the pictures Company Of Heroes 2 Video Game archive, you only need to click on the "Download" button, which is located just below the text. We have gathered a huge collection of images in excellent and high quality, so you can view the Company Of Heroes 2 Video Game wallpaper. You easely can install a Company Of Heroes 2 Video Game as background for your PC, laptop, tablet, phone, smartphone and other devices. New collection of pictures, images and wallpapers with Company Of Heroes 2 Video Game, in excellent quality, and more than 30 pictures in post. ![]() All pictures in Full HD specially for desktop PC, Android or iPhone. High definition and quality wallpaper and wallpapers, in high resolution, in HD and 1080p or 720p resolution Company Of Heroes 2 Video Game is free available on our web site. Download Company Of Heroes 2 Video Game wallpapers The company remains blinded to data from this arm and the trial continues in follow-up to allow the data to mature. The company will complete a full evaluation of the available CheckMate -649 data and work with investigators to share the results at an upcoming medical conference, as well as discuss them with health authorities.ĬheckMate -649 is also evaluating the Opdivo plus Yervoy (ipilimumab) combination compared to chemotherapy in patients with gastric cancer, GEJ cancer or esophageal adenocarcinoma. Teclistamab in Relapsed or Refractory Multiple Myeloma Clinical Decisions Screening for Atrial Fibrillation in Asymptomatic Older Adults Perspective Noncompete Agreements The Need for a Refresh. “We look forward to engaging health authorities worldwide with the goal of bringing this immunotherapy-based treatment option to patients as soon as possible.” Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. “The results from CheckMate -649, the largest study of gastric and esophageal cancers conducted to date, indicate the potential for Opdivo plus chemotherapy to change practice in the first-line setting and become a new standard of care for certain patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma,” said Ian M. “Immunotherapy helped transform how we care for our patients across different tumor types, and the encouraging results from CheckMate -649 represent a new opportunity to improve survival for patients beyond standard chemotherapy.” ![]() Janjigian, M.D., Principal Investigator, Chief, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center. Responses to the current standard chemotherapy in patients are short lived, and less than 6% of patients with metastatic disease survive beyond five years,” said Yelena Y. “There is an urgent need to improve therapeutic options for patients with esophageal and stomach cancer. The safety profiles of Opdivo and chemotherapy in this trial are reflective of the known safety profiles of Opdivo and chemotherapy in first-line gastric and esophageal cancers. Opdivo is the first and only PD-1 inhibitor to demonstrate superior OS and PFS in combination with chemotherapy when compared to chemotherapy alone in patients with gastric cancer, GEJ cancer or esophageal adenocarcinoma. The OS benefit was also observed in the all-randomized population. These results represent the first treatment advance in many years for these patients, potentially establishing adjuvant nivolumab as a new standard of care.Bristol Myers Squibb announced that CheckMate -649, a pivotal Phase 3 trial evaluating Opdivo (nivolumab) plus chemotherapy compared to chemotherapy alone as a first-line treatment for metastatic gastric cancer, gastroesophageal junction (GEJ) cancer or esophageal adenocarcinoma, met both primary endpoints of overall survival (OS) at a pre-specified interim analysis and progression-free survival (PFS) at final analysis in patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 5. Data including DFS rate and an analysis of DFS across pre-specified subgroups will be presented.Īdjuvant nivolumab is the first therapeutic to provide a statistically significant and clinically meaningful improvement in DFS vs placebo and a well-tolerated safety profile in patients with resected EC/GEJC, who have received neoadjuvant CRT. The frequency of serious TRAEs and TRAEs leading to discontinuation were ≤ 9% with nivolumab and 3% with placebo (Table). ![]() ![]() The majority of treatment-related adverse events (TRAEs) were grade 1 or 2. At a pre-specified interim analysis, adjuvant nivolumab showed a statistically significant improvement in DFS vs placebo (HR 0.69 P = 0.0003) median DFS was doubled (22.4 vs 11.0 mo, respectively Table). Approximately 70% of patients had adenocarcinoma and almost 60% had a pathologic lymph node status ≥ypN1 in both groups. Indication : Esophageal Cancer, Gastroesophageal junction cancerħ94 patients were randomized (nivolumab, 532 placebo, 262). |