Podcasts about LDR

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Best podcasts about LDR

Latest podcast episodes about LDR

LDR
LDR#519 - vom 11.04.2025

LDR

Play Episode Listen Later Apr 15, 2025 49:48


LDR#519 - vom 11.04.2025

Storytime
I Drove Through A Tornado For *** r/TodayIFuckedUp Reddit Stories

Storytime

Play Episode Listen Later Apr 14, 2025 29:44


r TIFU TIFU by accidentally ruining my LDR girlfriend's big surprise visit TIFU by joining the Mormon church TIFU by throwing away a child's teddy bear and having to dumpster dive TIFU by telling a stupid joke TIFU by literally forgetting my dang exam TIFU by giving my husband a playful pat TIFU by overdosing on herbal tea

Love is in the Air
#46 LDR KILLERS Part 2!

Love is in the Air

Play Episode Listen Later Apr 8, 2025 34:17


Join Abe and Elaine as they discuss more LDR killers

LDR
LDR#518 - vom 28.03.2025

LDR

Play Episode Listen Later Apr 1, 2025 55:43


LDR#518 - vom 28.03.2025

SparX by Mukesh Bansal
Money Podcast For Indians In Their 20s – Money, Inflation, Illusion & Economy | Neelkanth M | SparX

SparX by Mukesh Bansal

Play Episode Listen Later Mar 29, 2025 55:37


Is money real, or is it just an illusion we all believe in? In this episode, Neelkanth Mishra takes us through his journey with studying and understanding money. We explore the concept of money—how it started, why it holds value, and why it might not be as real as we think. Neelkanth challenges everything we assume about wealth, explaining how inflation, trust, and government policies shape our financial system. Watch till the end to rethink how you see money!Resource list - What is Fort Knox? - https://en.wikipedia.org/wiki/Fort_Knox Gold in Fort Knox - https://elements.visualcapitalist.com/how-much-gold-is-in-fort-knox/Bank run - https://www.investopedia.com/terms/b/bankrun.aspCRR - https://www.idfcfirstbank.com/finfirst-blogs/finance/what-is-crr What was the 2008 Financial crisis? - https://en.wikipedia.org/wiki/2008_financial_crisis https://www.britannica.com/money/financial-crisis-of-2007-2008Loan-to-Deposit ratio - https://www.investopedia.com/terms/l/loan-to-deposit-ratio.asp#:~:text=The%20loan%2Dto%2Ddeposit%20ratio%20(LDR)%20helps%20you,expressing%20it%20as%20a%20percentage. Open market operations - https://www.investopedia.com/terms/o/openmarketoperations.asp Currency in circulation - https://www.investopedia.com/terms/c/currency-in-circulation.asp#:~:text=Currency%20in%20circulation%20is%20all,in%20checking%20and%20savings%20accounts.What is EBLR? - https://www.kotak.com/en/stories-in-focus/loans/home-loan/eblr-interest-rate.html What is CBDC? - https://www.investopedia.com/terms/c/central-bank-digital-currency-cbdc.asp How can RBI contain rupee depreciation? - https://www.icicidirect.com/research/equity/finace/how-can-rbi-contain-rupee-depreciation 

Curhat Babu
Raim Laode: Arti Bahagia dan Berbakti

Curhat Babu

Play Episode Listen Later Mar 26, 2025 44:35


Memperjuangkan hubungan jarak jauh rasanya mustahil bagi sebagian orang. Tapi, Raim dan Komang berhasil meraih akhir bahagia mereka sebagai pasangan dan juga orang tua. Yuk simak naik turun perjalanan Raim dan Komang dalam memperjuangkan kebahagiaan di Podcast Curhat Babu!Timestamp:00:01 Opening04:15 LDR adalah momen seleksi07:54 Upgrade bahagia oleh Tuhan10:28 Hal terberat sebagai kepala rumah tangga14:15 Pentingnya merawat jarak20:05 Perbedaan rasa saat LDM dan LDR 32:05 Makna berbakti pada orang tua bagi Raim Laode

SparX by Mukesh Bansal
The REAL Truth Of Indian Economy - Stock Market, GDP & Trump Effect | Neelkanth M | SparX by Mukesh Bansal

SparX by Mukesh Bansal

Play Episode Listen Later Mar 22, 2025 72:48


In this episode of SparX, we dive deep into the complexities of the global economy, India's growth trajectory, and the impact of Trump's return to power. Neelkanth Mishra breaks down why forecasting the economy is as tough as predicting the weather, how crowd behavior shapes policy, and why AI is disrupting global markets.We discuss India's economic challenges—monetary tightening, regulatory hurdles, and geopolitical shifts—while exploring potential solutions for achieving 7%+ growth. Are global markets headed for a crisis? How will AI reshape economic structures? And can India leverage this disruption to its advantage?Resource List - US President Trump and Ukraine President Zelensky - https://youtu.be/ajxSWocbye8?feature=shared Nixon and Kissinger meeting Indira Gandhi - https://history.state.gov/historicaldocuments/frus1969-76ve07/d135 https://www.ndtv.com/india-news/henry-kissinger-indira-gandhi-when-henry-kissinger-called-indira-gandhi-a-b-h-indians-bastards-4619944 The Great Transformation, book by Odd Arne Westad and Jian Chen - https://amzn.in/d/0QllE5P India's Quantitative Tightening by Neelkanth Mishra - https://tessellatum.in/?p=478 What is the Overton Window? - https://www.mackinac.org/OvertonWindow More on Mrs. Watanabe - https://en.wikipedia.org/wiki/Mrs._Watanabe https://www.linkedin.com/pulse/rise-mrs-watanabe-how-japanese-housewives-became-force-moenga-alex-akg6f What is fiscal deficit? - https://economictimes.indiatimes.com/definition/fiscal-deficit?from=mdr What is base money injection? - https://www.investopedia.com/terms/m/monetarybase.asp#:~:text=The%20money%20that%20they%20provide,of%20the%20Federal%20Reserve%20System. What is loan deposit ratio? - https://www.investopedia.com/terms/l/loan-to-deposit-ratio.asp#:~:text=The%20loan%2Dto%2Ddeposit%20ratio%20(LDR)%20helps%20you,expressing%20it%20as%20a%20percentage.

LDR
LDR#517 - vom 14.03.2025

LDR

Play Episode Listen Later Mar 17, 2025 51:26


LDR#517 - vom 14.03.2025

The Prostate Health Podcast
107: The Expanding Role for Modern Low Dose Rate (LDR) Prostate Brachytherapy – Steven Kurtzman, MD and Ankit Agarwal, MD

The Prostate Health Podcast

Play Episode Listen Later Mar 13, 2025 26:51


We are delighted to partner with Western Radiation Oncology today, with two of their distinguished radiation oncologists joining us on the Prostate Health Podcast.  LDR (Low Dose Rate) prostate brachytherapy has recently been an underutilized treatment for prostate cancer. However, advancements in modern techniques have demonstrated that LDR brachytherapy, a procedure that can be performed quite easily in an ambulatory surgery center, offers high cure rates with minimal long-term complications, making it a convenient, non-invasive option for men with prostate cancer. Today, we chat with Dr. Steven Kurtzman and Dr. Ankit Agarwal, two distinguished radiation oncologists working to expand access to LDR brachytherapy by partnering with urologists to establish new programs across the United States.  Drs. Kurtzman and Agarwal are national leaders in targeted real-time intraoperative planned brachytherapy. With over 7,000 implants performed in the past two decades and more than 700 procedures conducted annually, they have managed to preserve this specialized technique despite its limited expansion in recent years. Based primarily in the Bay Area, California, they provide exceptional cancer care while collaborating with urologists, medical oncologists, and prostate cancer specialists across the United States to assist in establishing LDR programs in ambulatory surgery centers nationwide to provide high-quality prostate cancer care. Tune in to learn more about this promising treatment option! Disclaimer: The Prostate Health Podcast is for informational purposes only. Nothing in this podcast should be construed as medical advice. By listening to the podcast, no physician-patient relationship has been formed. For more information and counseling, you must contact your personal physician or urologist with questions about your unique situation. Show Highlights: Who are the most viable candidates for LDR brachytherapy? How the treatments for low, intermediate, and high-risk prostate cancer patients differ The benefits of a combination of brachytherapy and external beam radiation for high-risk prostate cancer patients How factors like urinary function, bowel function, and prostate size can influence men's eligibility for LDR brachytherapy Why prostate size is no longer a limitation for brachytherapy treatment How is the LDR brachytherapy procedure performed? What can patients expect in terms of recovery and side effects following brachytherapy? Post-therapy safety precautions Links:  Follow Dr. Pohlman on Twitter and Instagram - @gpohlmanmd  Get your free What To Expect Guide (or find the link on our podcast website)   Join our Facebook group  Follow Dr. Pohlman on Twitter and Instagram  Go to the Prostate Health Academy to sign up.  You can access Dr. Pohlman's free mini webinar, where he discusses his top three tips to promote men's prostate health, longevity, and quality of life here. Sponsor Links:  Western Radiation Oncology Brachytherapy for Prostate Cancer with Dr. Steven Kurtzman and Dr. Ankit Agarwal on YouTube Expanding Treatment Options at Ambulatory Surgical Centers: LDR Brachytherapy for Prostate Cancer    

LDR
LDR#516 - vom 28.02.2025

LDR

Play Episode Listen Later Mar 5, 2025


- Am 23.2.2025 wurde der Bundestag gewählt! Wir blicken mit Moritz Warnke, Referent für soziale Infrastruktur und verbindende Klassenpolitik der Rosa-Luxemburg-Stiftung auf das Ergebnis. Wurde die CDU Wahlsieger "ohne Glamour" überraschte die erneuerte Linke einen Achtungserfolg. Die extrem rechte AfD verdoppelte ihr Ergebnis, vor allem im Osten ist die Karte blau. Kann Die Linke ein Pol gegen die Faschisierung sein? Wie sind die Wahlergebnisse zu lesen und zu interpretieren? Das und mehr im Gespräch. - ein wenig Sachsen, wie üblich im Nachschlag.

Loving BDSM
Q&A: What Should We Negotiate and Decide Before We Move In Together?

Loving BDSM

Play Episode Listen Later Mar 3, 2025 23:55 Transcription Available


They're thinking of moving in together and want to make sure they plan appropriately. Here's the question: I am a newer submissive who's in a LDR with a Daddy Dom. We have met several... The post Q&A: What Should We Negotiate and Decide Before We Move In Together? appeared first on Loving BDSM.

The Daily Ketchup
Are Men Just Trying To Get LAID On Valentine's Day?

The Daily Ketchup

Play Episode Listen Later Feb 10, 2025 32:13


What are the 3 RULES to find the perfect Valentine's gift? Is SEX the end goal for men on Valentine's Day? Why is proposing on Valentine's Day a BIG MISTAKE?In today's podcast, we discuss the most hotly debated Valentine's Day topics, including the relationship dynamics between men and women in the context of intimacy, LDR date ideas for taking your long-distance relationship to the next level, and why there should be no excuse for forgetting Valentine's Day in 2025.#valentinesday #valentine #valentinesday2025 #valentines #14feb #vday #singapore #dailyketchup Hosted on Acast. See acast.com/privacy for more information.

Love is in the Air
#45 How a LDR changes you!

Love is in the Air

Play Episode Listen Later Feb 4, 2025 38:15


Join Elaine and Abe as they discuss how being in a LDR or commuter marriage changes you for the worse and for the better! Ultimately if you push through the worse it all becomes a positive change and strengthens you anyway! ❤️The book Elaine referenceshttps://amzn.to/42JjPmo

LDR
LDR#515 - vom 31.01.2025

LDR

Play Episode Listen Later Feb 2, 2025 54:13


LDR#515 - vom 31.01.2025

Podcast Campus
Eps 7 | S7 | LDR Dadakan : Dari Satu Kampus ke Jarak Jauh Saat Liburan

Podcast Campus

Play Episode Listen Later Jan 25, 2025 25:01


Between the Pew
LDR Weekend 2025 PRE-CAP

Between the Pew

Play Episode Listen Later Jan 24, 2025 37:55


Hear Charles and Kellie talk about all the details for LDR Weekend 2025 and find out how to register now! Link for LDR registration: https://aampca.org/conference/

All Ears: The Team World Vision Podcast

We're back! And we're remembering and reflecting on our "why" as the one and only LDR takes us through a time of reflection.

LDR
LDR#514 - vom 17.01.2025

LDR

Play Episode Listen Later Jan 22, 2025 50:36


LDR#514 - vom 17.01.2025

LDR
LDR#513 - vom 03.01.2025

LDR

Play Episode Listen Later Jan 7, 2025 51:13


LDR#513 - vom 03.01.2025

LDR
LDR#512 - vom 20.12.2024

LDR

Play Episode Listen Later Dec 27, 2024 53:22


LDR#512 - vom 20.12.2024

The Liberal Dan Radio Program
Hunter Biden is, rightly, pardoned.

The Liberal Dan Radio Program

Play Episode Listen Later Dec 3, 2024 111:00


Since BTR is going AFK PDQ, join LDR on youtube. 

Stompcast
Pt 3: Why a Year Apart Made My Relationship Stronger | Hardest Geezer

Stompcast

Play Episode Listen Later Nov 27, 2024 16:17


As long distance running meets long distance relationships, in part 3, Russ Cook (Hardest Geezer) explains how he and his girlfriend stayed connected during a year away. Russ shares a top tip for anyone in a LDR, how he grew spiritually during his challenge and he reveals the terrifying story of when he got kidnapped. Plus, when Dr Alex asks about Russ' new normal, it reveals how the mental impact of the challenge is still ongoing…Follow @hardestgeezer and get his new book ‘Mind Over Miles' Follow the podcast on Instagram @thestompcastTo improve your mental fitness, get Dr Alex's book The Mind ManualDownload Mettle: the mental fitness app for men Hosted on Acast. See acast.com/privacy for more information.

Love is in the Air
#44 The BIG and everyday SACRIFICES of Being in a LDR!

Love is in the Air

Play Episode Listen Later Nov 18, 2024 42:11


Join Abe and Elaine as they dive into the everyday sacrifices that define life in a long-distance relationship (LDR). Celebrate the resilience, commitment, and growth that come from navigating love across the miles. Whether you're in an LDR or simply curious about what it takes, discover how these sacrifices not only strengthen your bond but also enrich your character and relationship in ways you never imagined. Be proud of the love story you're creating—one challenge at a time!

The CLS Experience with Craig Siegel
Just Getting Warmed Up With World Record Holder Jenny Hitchings

The CLS Experience with Craig Siegel

Play Episode Listen Later Oct 28, 2024 51:47


It's my favorite week of the year - The NYC Marathon is this Sunday and I will be entering the arena to compete once again. In honor of that we have the perfect guest. Legendary distance runner Jenny Hitchings joins us to share her remarkable journey, transforming from a college fitness enthusiast to a record-setting athlete in her 50s and 60s. Jenny's story is proof that it's never too late to bloom and that relentless dedication can lead to extraordinary results. Let's dive in.On today's episode of The CLS Experience, we have a very exclusive treat. She's a legendary distance runner and a record-setting powerhouse in the running world. She's the Age Group 55-59 and 60-64 Marathon World Record Holder, and she holds eight Age Group American Records in distances such as the 5K, 10 mile, 10k, ½ Marathon, and Marathon, and seven American Records for the 60-64 age group, Just to name a few. Recognized as a multi time USATF Overall Female Road Runner of the Year, and the Masters Long Distance Athlete of the Year, she was inducted into the USATF Masters Hall of Fame in 2021, no big deal.  Additionally, she was honored as the LDR and RRCA Open Runner of the Year in 2023, BIG facts. She's just a juggernaut in all facets of life and a terrific human being. Please welcome the unstoppable, inspiring, and limitless, the beautiful and gritty Jenny Hitchings.   7:55 – Chasing Speed and Success 17:20  – Mastering Nutrition, Recovery, and Handling Pressure 27:45  – Shifting Sponsorship Perceptions in Running 39:25 – Overcoming Running Challenges 44:37  – The London Marathon and Finding Joy in Life 50:30 – The Parallels Between Running and LifeTo join our community click here.➤ To connect with Jenny Hitchings follow Jenny on Instagram➤ Order a copy of my new book The Reinvention Formula today! ➤ Join our CLS texting community for free daily inspiration and business strategies to elevate your day, text (917) 634-3796To follow The CLS Experience and connect with Craig on Social Media:➤ INSTAGRAM➤ FACEBOOK➤ TIKTOK➤ YOUTUBE➤ WEBSITE➤ LINKEDIN➤ TWITTER

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 100 "The Hidden Costs of an LDR" with Alex Calleja

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later Oct 27, 2024 81:10


We have arrived at Episode 100! It's Part 2 of our 3 episode set of the podcast with Mo and Alex! Caller #3 is Micay who is 38yrs old from Manila.  Micay is involved with a married guy from Los Angeles who is offering to give her 35k.  She knows she has to cut it off soon but should she wait for the cash before she blocks him? Caller #4 is TM who is 50yrs old from Germany.  TM is in an LDR with her long time partner but pre-menopause has her sex drive running high.  She tried an escort service in Amsterdam and it unlocked her. We will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 99 "Bad Boyfriends or Stupid Girlfriends?" with Alex Calleja

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later Oct 26, 2024 82:19


We have a hilarious back-to-back-to-back episode set with Mo and Alex here and we surpass 100 episodes for this Year 13 of GTWM. Let's not delay! Caller #1 Peach 27yrs old from Manila.  Peach and her fiance are in an LDR, so to satisfy their sexual needs, her husband wants her to hook up with guys while he watches the act via livestream. Caller #2 is Marie who is 31yrs old from Vancouver.  Marie is dating a married man who got both his wife and her pregnant simultaneously.  She has since had a miscarriage, and she wants him to choose between her and his wife. We will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

Love is in the Air
#43 Closing the Distance in the US!

Love is in the Air

Play Episode Listen Later Sep 16, 2024 54:51


Join Elaine and Abe as they interview awesome guests ❤️Jaime and Lisa❤️who have closed the distance in the US! Hear what they have to say to inspire and motivate you to hang on in distance. Their input inspired  Elaine to make an exhaustive list of what to take care of before you close your distance when you move from state to state. Get ready to take some notes but we will also post these lists on our IG support page: @ instagram.com/commutermarriagesupport. In the future Elaine and Abe will interview couples closing the distance from country to country.

World Nuclear News
The Finnish SMR designed to produce heat, not electricity

World Nuclear News

Play Episode Listen Later Aug 23, 2024 29:22


Steady Energy is developing the LDR-50 small modular reactor with the initial goal of decarbonising district heating systems. The CEO of the Finnish company, Tommi Nyman, explains why the decision to focus on heat rather than electricity was taken.The company was spun out of VTT, Finland's national research lab, and was prompted by its researchers noting that 10% of CO2 emissions come from heating water or steam to 150C and thinking "why not build something simple that would only cover low temperature heat markets". "In the context of the climate crisis, nuclear is a very good option, but the problem has been getting projects economically sound so that nuclear can be utilised without large subsidies. We know that the most economical way to use nuclear is just to generate thermal energy without using the heat to create electricity," he tells host Alex Hunt. Nyman added that simplicity has been key to their design, "by only producing heat you can reduce the amount of equipment in a nuclear power plant by 50%". The cost of energy they are aiming at is below EUR40 per MWh, depending on how the utility wants to operate it and the aim is to have a first plant delivered in 2030.Also in this episode World Nuclear News's Claire Maden reports on events in India, South Africa and uranium developments in the USA and Australia.Key links to find out more:World Nuclear NewsFinnish municipal decision-makers favourable to SMRsIndia's NTPC confirms plans for nuclear subsidiarySouth Africa pauses nuclear procurement processEmail newsletter:Sign up to the World Nuclear News daily or weekly news round-upsContact info:alex.hunt@world-nuclear.orgEpisode credit:  Presenter Alex Hunt. Co-produced and mixed by Pixelkisser Production 

Love Strategies: Dating and Relationship Advice for Successful Women
The Truth About Long Distance Relationships: What Science Says

Love Strategies: Dating and Relationship Advice for Successful Women

Play Episode Listen Later Aug 12, 2024 36:32


Originally aired: April 9th, 2023Thanks to the internet, long-distance relationships (LDRs) have become a popular phenomenon. From spousal separations to meeting someone special online, LDRs are now more common than ever before. But how do you make it work?In this podcast, we share personal experiences and expert advice on navigating the challenges of long-distance love. We ask the most important question: Will it work? We discuss the risks involved in investing in a long-distance relationship and the role that distance plays in creating desire.Join us as we explore different scenarios where we might recommend pursuing an LDR, and discuss strategies for making it work. We'll cover topics like quality time versus constant quantity, having a plan to live near each other within a year, and spending more than just a weekend together.NEXT STEP: Book a complimentary Love Strategy Session and let us help you attract love this year: https://go.lovestrategies.com/session

The Vtwin Life
milepost 134 Maurice Jester

The Vtwin Life

Play Episode Listen Later Aug 9, 2024 64:56


Milepost 134 Maurice Jester
It's been honor to introduce another rider to the LDR community and to the amazing organization that I talk so much about Mile Monsters Inc. So sit back and I'm enjoy this awesome milepost. Want to help support the channel check out my social media pages and follow there as well

Leaguecast: a League of Legends Podcast

The boys discuss T1's world skins, Tyler1 co-streaming LCS, LDR vs Mortal Reminder, and more on episode 652 of Leaguecast! Email us - mail@leaguecastpodcast.com   Support us - https://www.patreon.com/leaguecast  Tweet us - https://twitter.com/leaguecast   Facebook - https://www.facebook.com/Leaguecast/   Join Our Discord - https://discord.gg/leaguecast  Visit our Website - https://leaguecastpodcast.com/ 

9 to 5ish with theSkimm
Venus et Fleur Founder Seema Bansal Chadha on Protecting Your Customer

9 to 5ish with theSkimm

Play Episode Listen Later Jul 24, 2024 30:41


When Seema Bansal Chadha was in her early twenties, she was in a very new, long distance relationship with a guy named Sunny. In classic LDR-status, he sent her flowers for Valentine's Day. It was supposed to be a romantic gesture, but the flowers arrived wilted. NBD though. The  flop would lead Seema to move to New York to be with Sunny…and to co-found Venus et Fleur with him too.  In this episode of 9 to 5ish, Seema shares:  Why her father's lighting and plumbing store informed her own entrepreneurship How she rationalized starting a biz with her boyfriend of less than a year The moment Venus et Fleur blew up (shout out to the Kardashians) How the hustle of the early days compares to the hustle now Why protecting your existing customers sometimes outweighs trying to attract new ones

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 62 "Love Lines: From LDR's to Divorce Decisions and Family Feuds" with Alex Calleja and Sam Oh

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later Jul 8, 2024 104:41


Let's kick off a brand-new week with another Mo, Alex and Sam trio! And a trio it is with 3 thirtysomethings calling for today's slate. It should be a fun time! Don't forget to rep your GTWM gear by checking out the official GTWM Merch store at gtwmpodcast.myshopify.com Caller #1 is Wyla who is 35yrs old from Chicago.  Wyla is in the US short term but she thinks she has found a long-term love.  She hates the LDR setup but is it possible to have both worlds? Caller #2 is Anne who is 37yrs old from Singapore.  Anne is so close to divorce due to her husband's inability to communicate.  Is it really him or perhaps the environment she creates? Caller #3 is Maris who is 35yrs old from Manila.  Maris is adopted and now having daddy issues.  Should she tolerate her dad's shit behavior if her mom allows it?  Or does she get involved because wrong is wrong. Powered by Spotify, we will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

Relationsh!t
Long Distance Sh!t

Relationsh!t

Play Episode Play 30 sec Highlight Listen Later Jun 19, 2024 103:22


We are absolutely obsessed with this week's #QueerRelationshipGoals, husbands Wesley and Derrick (@willis_partyoftwo) - as they are pretty perfect in just about every way. Black love, romance, adventure, and just about everything you could want in a relationship, these guys are the truest definition of inspirational and aspirational. We enjoy them and know you will! Go give them a follow on IG and let them know the Critellis sent you. Then, the guys sit down to talk about their experiences with long distance relationships and whether or not they think they can work. Could you successfully see an LDR through? What circumstances would have to be in place for you to willingly enter a long distance relationship? Marko and Tony explore this topic. Finally, @thecritellis read this week's Listener Sh!tuation and do their best to give some guidance, Critelli-style.Articles:Self Mastery Central: Long Distance Relationship Statistics That You Didn't KnowShit to Put on Your Radar:Marko and Tony are taking the months of July and August off, so June 26th will be their last live-recorded episode of the season. Join the guys for season 10 of the podcast, dropping on Wednesday, September 11th. See you there!If you could use some mental clarity, natural energy, and enhanced productivity, then we totally recommend you try Magic Mind! You can get it at: www.magicmind.com/relation. With RELATION20 you also get up to 56% off your first subscription or 20% off your one-time purchase - it also works if you're already a subscriber! You save on your next subscription payment.Get all your shave and beard needs by visiting www.proraso-usa.com and using code RELATIONSHIT15 at checkout, and get 15% off your purchase! Support the Show.Sh!t | Leave us a voicemail with your relationship sh!tuation at (903) POD- SHIT. That's (903) 763-7448. You can also fill out a Listener Sh!tuation on our website, podrelationshit.com, or email us at relationshitquestions@gmail.com. Visit Us |www.podrelationshit.com for more Relationsh!t content and information about the podcast.Donate | Head over to patreon.com/podrelationshit and start donating today! Your donations will give you early access to the podcast, behind-the-scenes interviews with our weekly guests, and merchandise.Rate Us | Go to your favorite podcast directory and give Relationsh!t a 5-Star rating, and a fantastic review!Follow Us | Instagram, Twitter, and Facebook: @podrelationshitAnd follow Marko and Tony on Instagram (@thecritellis) if you want a BTS look into their relationship and adventures!

ASCO Daily News
Immunotherapy at ASCO24: NADINA and Other Key Studies

ASCO Daily News

Play Episode Listen Later Jun 19, 2024 34:51


Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, thank you.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Love is in the Air
#41 LDR KILLERS: What Kills a Long Distance Relationship!

Love is in the Air

Play Episode Listen Later Jun 13, 2024 37:48


Join Abe and Elaine in the ongoing series to discuss LDR killers!

Reimagining Love
Strategies for a Thriving Long-Distance Relationship (Re-release)

Reimagining Love

Play Episode Listen Later Jun 4, 2024 64:51


Long-distance relationships are no walk in the park, but that doesn't mean they can't thrive. In this episode, Dr. Alexandra tackles this topic, sharing tools and tips for couples. If you and your partner live in different time zones, are pros at FaceTime dates, and are constantly asking, "when's our next visit?", this episode is for you.Relevant links:Access the Long-Distance Relationships worksheet hereOrder Dr. Alexandra's new book, Love Every DaySubscribe to Dr. Alexandra's NewsletterSubmit a Listener QuestionTake Dr. Alexandra's "Relationship Superpower" Quiz Join Dr. Alexandra's five-day retreat with the Modern Elder Academy — Get 10% off with code 'GF10'

Hush Podcast
LDR, is it really possible? ft. Saffron Sharpe

Hush Podcast

Play Episode Listen Later Jun 4, 2024 31:53 Transcription Available


Long distance relationships. It's a connection many of us have pondered: Can you truly connect with someone who's miles and miles away from you and find genuine love? Sure, we've all heard the success stories of LDRs, but they say it's not for the faint of heart. How does it actually work? In this episode, the Hush girls and their guest, Saffron Sharpe, who recently met her boyfriend while on holiday, will dive into the possibilities and realities of forming meaningful connections across the world as Saffron shares her love story! Watch this episode on YouTube: https://youtu.be/_3_r8tTrPwESee omnystudio.com/listener for privacy information.

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 44 "Sendwaving" with Hydee Pichai

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later May 31, 2024 73:22


We are wrapping up a big month partnership with Sendwave this May and we had a blast highlighting how easy it is to send money to your family in the Philippines via the Sendwave app!  Awesome exchange rates, options to use Gcash or a bank account, quick and trusted flow of money from the US, Canada, and certain countries in Europe -- Sendwave is a game changer in the industry.  We have the first Sendwave ambassador Hydee Pichai on the podcast tonight talking to our callers from all over North America about their love and life issues.  Let's go! Caller #1 is Roxanne who is 31yrs old from New York.  Roxanne's boyfriend follows hot and scantily clad IG girls and it's been bothering her.  She told him if he continues to do so, there will be no sex for him -- so she checks his IG account before every deed. Caller #2 is Claire who is 27yrs old from Quebec.  Claire had a boyfriend who was also attached to another girlfriend in an LDR setup.  On a recent "vacation trip" to the Philippines, she found out on Facebook that he was getting married. Caller #3 is AJ who is 33yrs old from Toronto.  AJ is planning to marry her girlfriend but because she is in the LGBTQ community and her parents are INC, she is unsure if it will ruin their relationship. Powered by Spotify, we will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Send in a voice message: https://podcasters.spotify.com/pod/show/djmotwister/message Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

The TMZ Swift-Tea
Taylor Swift Joining The Marvel Cinematic Universe?

The TMZ Swift-Tea

Play Episode Listen Later May 24, 2024 33:19


Happy Friday SWIFTIES! We have guest host Shy Taylor back with us to discuss some pretty hot topics. One iof them we devour for lunch. And yes we're looking at you Bullie Ellish. She's gone to far and we can only assume Taylor has got BE scared. Plus wtf LDR!! We break down why the chiefs are back to practice with TMZ Sports Edward Lewis and whether or not Taylor had an impact on the KC Chiefs' schedule! Hosts: Melanie Miller & Shy Taylor Learn more about your ad choices. Visit megaphone.fm/adchoices

Gals on the Go
juicy polls with TK

Gals on the Go

Play Episode Listen Later May 22, 2024 89:09


It's time to get juicy with TKsjuicypolls this week! The gals welcome Taylor King (TK) to the pod and turn the tables by asking her some poll questions. LDR forever or single forever? Settling down in your hometown or far away? What's more intimate, cuddling or sex? If you want to know what the gals have to say, tune in. Brooke and Danielle also chat about Danielle's jewelry collection with Electric Picks and the Miccio Family trip to Italy! Please support our show by checking out our sponsors! Rhoback: Use the code GALS on Rhoback.com for a generous 20% off your first order through the end of this week. BetterHelp: This show is sponsored by BetterHelp! Visit BetterHelp.com/gals to get 10% off your first month of online therapy Gametime: Take the guesswork out of buying tickets with Gametime. Download the Gametime app, create an account, and use code GALSONTHEGO for $20 off your first purchase. Squarespace: Go to www.squarespace.com/gals to save 10% off your first purchase of a website or domain Honeylove: Treat yourself to the best bras on the market and save 20% off at honeylove.com/Gals20

Girls Gotta Eat
Don't Wait for a Partner to Do the Damn Thing!

Girls Gotta Eat

Play Episode Listen Later May 13, 2024 94:17


If you feel like everyone around you is partnered up and you're missing out on doing things because you're single – this episode is for you! We are encouraging you to live the life you want (and deserve) regardless of your relationship status and are giving tips for doing it – everything from traveling solo to making more friends to doing home improvements. We also discuss going out to eat alone, the joy of buying expensive things for yourself, and the milestones our listeners have accomplished on their own. Before we get into the topic, we are recapping VEGAS (the Lovers & Friends festival getting canceled and Rayna's hot date), Ashley's LDR realizations, and a new addition to our family (!!!). Hope you enjoy! Follow us on Instagram @girlsgottaeatpodcast, Ashley @ashhess, and Rayna @rayna.greenberg. Visit our website for tour dates, merchandise, and more. Enter the Vibes Only giveaway. Thank you to our partners this week: Nutrafol: Get $10 off your first month's subscription and free shipping at nutrafol.com with code GGE. Helix: Get 30% off all mattress orders plus two free pillows at helixsleep.com/gge. Skims: Shop the Skims T-Shirt Shop at skims.com.  ZocDoc: Download the Zocdoc app to sign-up for free and book a top-rated doctor at zocdoc.com/gge. 

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 32 "Who's Your Daddy?" with Alex Calleja and Angelicopter

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later May 8, 2024 77:16


Back-to-back AMA? Let's go!  Mo, Alex, and Chopper are ready to take on all of the chaos in the world with two straight episodes of GTWM.  Once again, there's a lot to learn about love and life in these shows so stick around for some laughter, lessons, and even a chance for two winners to take home $500 US Dollars courtesy of Sendwave! Caller #1 is D who is 37yrs old from Manila.  D cheated on her husband and now has a 5-month-old baby and she is seriously confused on who the baby's daddy is. Caller #2 is Amari who is 33yrs old from Sydney.  Amari is in an LDR with her husband.  The last few times she saw him, he refused to have sex.  He has a planned trip to Sydney coming up and she is wondering how she can have mind-blowing moments in the bedroom or will he say no again? Powered by Spotify, we will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Send in a voice message: https://podcasters.spotify.com/pod/show/djmotwister/message Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

OPENHOUSE with Louise Rumball
155 - [SOLO] - Long Distance Relation-Tips ft. Louise Rumball

OPENHOUSE with Louise Rumball

Play Episode Listen Later May 7, 2024 27:57


From the dreaded airport goodbyes to the joyous reunions, long distance relationships (LDR) can be HARD and EMOTIONALLY DRAINING. Add an anxious attachment style into the mix and you have the recipe for a rough ride ahead. Who are you with? Who are you f**king? What drugs are you taking? We've all at one point or another had these uncomfortable thoughts in an LDR but when managed well? They can also be beautiful, powerful testaments to a relationship that is worth going the long distance for! In today's solo episode, Louise dives headfirst into the wild world of long-distance relationships to arm you with the tips and tricks you need to make your long distance love thrive across miles and time zones.  In this episode, Louise spills the tea on:  Her personal experience of navigating her 2-year long distance relationship. Managing communication and staying emotionally connected. The importance of maintaining trust in an LDR. The power of thoughtful gestures. The 9 tips she swears by to hack the long distance game + to keep the romance alive. Facetiming fatigue and how you can spice things up in other ways. Her straight-out-of-a-movie ultimate meet cute with her boyfriend. And more! So if you're currently in a long-distance relationship or considering taking the plunge, this episode is your ULTIMATE survival guide. It's fast, it's fun, and you get Louise all to yourself with plenty of heartfelt advice from someone who's been there, done that, and still believes that love knows no bounds! ----- Ready to learn how to level up your life via your nervous system and subconscious mind in just 9 weeks? ⭐Join the There She Glows Waitlist⭐: https://www.thisisopenhouse.com/how-to-rewire-your-subconscious-mind  Join OPENHOUSE PREMIUM now at: https://openhouse.supercast.com/ Connect with Louise on Instagram: @iamlouiserumball Follow Louise (The Therapy Girl) on TikTok: @thetherapygirl__ Connect with OPENHOUSE on Instagram: @theopenhousepodcast Vibe With Me by Joakim Karud http://soundcloud.com/joakimkarud Music promoted by Audio Library https://youtu.be/-7YDBIGCXs Learn more about your ad choices. Visit podcastchoices.com/adchoices

Love is in the Air
#40 Which “Part” of You is Driving the LDR Bus?

Love is in the Air

Play Episode Listen Later Apr 5, 2024 49:35


We are on a unique journey being in a LDR or commuter marriage. ❤️✈️Sometimes it's like driving a bus

QuadShot News Podcast
3.25.2024 - GU003

QuadShot News Podcast

Play Episode Listen Later Mar 25, 2024 10:35


Check out this week's QuadCast where we highlight omission of the low neck in nasopharyngeal radiation treatment, the benefits of HDR boost over LDR boost for prostate cancer, and more.Check out the website and subscribe to the newsletter!   www.quadshotnews.com   Founders & Lead Authors: Laura Dover & Caleb Dulaney   Podcast Host: Sam Marcrom

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 21 "Long Distance Relationshit" with Sam Oh and Nikko Ramos

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later Mar 24, 2024 78:44


BSE is back with a Mo, Sam, Nikko trio that makes this episode perfect for download while you make that long trip to wherever this Holy Week.  We have 3 calls from all over the world, checking out what real life drama exists out there.  Let's do this! Caller #1 is Mar who is 28yrs old from Manila.  Mar and her boyfriend just LDR'd  but she is the type that likes to have spicy aggressive sex.  So now that he is gone until August, can she wait that long without some action? Caller #2 is Kenneth who is 31yrs old from Chicago.  Kenneth's wife track his phone, his car and himself have Apple Tags and he is bothered by all the lack of privacy considering he is totally faithful. Caller #3 is Sam who is 33yrs old from Los Angeles.  Sam has been with her boyfriend for 13 yrs and in their LDR challenge, she feels he is not making the extra effort to communicate properly.  Powered by Spotify, we will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Send in a voice message: https://podcasters.spotify.com/pod/show/djmotwister/message Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

Girls Gotta Eat
LONG-DISTANCE RELATIONSHIPS

Girls Gotta Eat

Play Episode Listen Later Mar 18, 2024 97:35


It's time for the long-awaited long-distance episode! We are talking all about long-distance relationships, covering the dos and don't, and sharing our experiences. We discuss trust, balancing travel and schedules, communication, ways to strengthen an LDR, signs that it's not going to work out, when is the right time for someone to move/discuss moving, sexting/phone sex, and more. Before we get into our topic, we catch up on Rayna's surgery and drug-induced purchases, Ashley's couples massage, and we answer the question “Has Love is Blind lost the plot?” Enjoy!  Follow us on Instagram @girlsgottaeatpodcast, Ashley @ashhess, and Rayna @rayna.greenberg. Visit our website for tour dates, merchandise, and more. Shop Vibes Only. Thank you to our partners this week: Clarins: Get 10% off, a free welcome gift, plus free shipping on your first order at clarins.com/gge. Chomps: Get 20% off your first order and free shipping at chomps.com/gge.  Nutrafol: Get $10 off your first month's subscription and free shipping at nutrafol.com with code GGE. ZocDoc: Go to zocdoc.com/gge and download the Zocdoc app to sign-up for FREE and book a top-rated doctor.

Good Times with Mo: The Podcast Year 10
GTWM Year 13 Episode 4 "Abusive LDR" with Alex Calleja and Angelicopter

Good Times with Mo: The Podcast Year 10

Play Episode Listen Later Jan 11, 2024 60:37


It's Part 2 of our back-to-back AMA for GTWM Year 13 Episode 5! Caller #3 is Lee who is 29yrs old from San Francisco.  Lee is a physically abusive LDR relationship.  Those words usually don't go hand in hand, but it makes it a bit more F'd up. Caller #4 is Ben who is 38yrs old from Los Angeles.  Ben needs drugs like ecstasy and poppers to enjoy sex.  Powered by Spotify, we will see you on another episode of GTWM tomorrow. Thanks for the download and please support the podcast by donating as little as $0.99 cents via Spotify --- Send in a voice message: https://podcasters.spotify.com/pod/show/djmotwister/message Support this podcast: https://podcasters.spotify.com/pod/show/djmotwister/support

The Bert Show
Would You Sign A Long Distance Relationship Contract?

The Bert Show

Play Episode Listen Later Aug 29, 2023 6:53


Would you ever do #LongDistance? Would it make you feel better if you had your partner sign a LDR contract?! Let's break it down! Learn more about your ad choices. Visit megaphone.fm/adchoices