Podcasts about her3

Featuring a slide presentation and related discussion from Dr Adrienne G Waks, including the following topics: Updated analyses from key studies of the 21-gene Recurrence Score® for localized ER-positive breast cancer (29:30) Four-year landmark analysis of the NATALEE trial of adjuvant ribociclib with nonsteroidal aromatase inhibitor for localized breast cancer (9:49) The PADMA trial of palbociclib with endocrine therapy compared to chemotherapy induction followed by endocrine therapy maintenance for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC) (11:25) Imlunestrant with or without abemaciclib for metastatic ER-positive mBC (13:18) TROP2-directed antibody-drug conjugates (ADCs) datopotamab deruxtecan and sacituzumab tirumotecan for HR-positive/HER2-negative mBC (17:50) Recent analyses from the DESTINY-Breast06 trial of trastuzumab deruxtecan (T-DXd) after endocrine therapy for HR-positive, HER2-low or HER2-ultralow mBC (21:09) The ICARUS-BREAST01 Phase II trial of the HER3-targeted ADC patritumab deruxtecan for HR-positive/HER2-negative mBC (26:02) Updates from neoadjuvant/adjuvant trials of pembrolizumab (KEYNOTE-522) and atezolizumab (NSABP B-59/GBG 96-GeparDouze) for localized triple-negative breast cancer (TNBC) (27:36) Ten-year update of the OlympiA trial of adjuvant olaparib for patients with germline BRCA1/2-mutated HER2-negative localized breast cancer (31:23) Exploratory analysis of patients who did or did not receive prior PD-1/PD-L1 inhibition in the Phase III OptiTROP-Breast01 study of sacituzumab tirumotecan versus chemotherapy for previously treated advanced TNBC (32:56) CNS efficacy of T-DXd (DESTINY-Breast12 trial) and outcomes with palbociclib combined with anti-HER2 therapy (AFT-38 PATINA trial) for HER2-positive mBC (34:04) CME information and select publications

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/interprofessional-monitoring-and-management-of-aes-with-her3-directed-adcs/26458/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/overcoming-egfr-resistance-with-her3-directed-adcs/26457/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/biologic-rationale-for-targeting-her3-and-role-in-egfr-resistance/26456/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/expert-peer-discussion-integrating-novel-her3-directed-adcs-upon-disease-progression-following-egfr-tki-and-platinum-chemotherapy/26455/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/case-application-patients-with-egfrm-resistance-post-tki-and-platinum-chemotherapy/26454/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

CME credits: 0.75 Valid until: 17-12-2025 Claim your CME credit at https://reachmd.com/programs/cme/case-application-patients-with-egfrm-resistance-post-tki-and-platinum-chemotherapy/26453/ This 6-episode program will guide healthcare professionals who treat advanced non-small cell lung cancer (NSCLC) through the biology of HER3 overexpression to broaden their understanding of its potential as a therapeutic target in EGFR-resistant advanced NSCLC. Tune in to enhance your confidence in applying scientific evidence to the creation of effective treatment strategies and develop evidence-based approaches for implementing novel HER3-directed antibody-drug conjugates (ADCs). Our experts also focus on the adoption of a team-based approach to help you monitor and manage treatment-related adverse events associated with HER3-directed ADCs.

“Key thing here is that it was discovered that when you have gene amplification of her two you get a resultant over expression of that HER protein and that over expression leads to a driver for certain cancers. So, when you have an over expression of HER2 it leads to the cancer being more aggressive,” ONS member Rowena “Moe” Schwartz, PharmD, BCOP, FHOP, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about HER inhibitors.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0   Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by December 13, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation.  Learning outcome: The learner will report an increase in knowledge related to HER inhibitor drugs.  Episode Notes   Complete this evaluation for free NCPD.   Oncology Nursing Podcast™ Pharmacology 101 series   ONS Voice articles:  Antibody–Drug Conjugates Join the Best of Two Worlds Into One New Treatment  HER2 Therapies May Be Effective in a Variety of Solid Tumors  Management Strategies for Cutaneous Toxicity From EGFR Inhibitors  Manage Common Ocular Toxicities From Tyrosine Kinase Inhibitors  Oncology Drug Reference Sheet: Combination Trastuzumab and Hyaluronidase-Oysk  Oncology Drug Reference Sheet: Elacestrant  Oncology Drug Reference Sheet: Margetuximab-Cmkb  Oncology Drug Reference Sheet: Talazoparib  ONS book: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (Second Edition)   ONS courses:  ONS Cancer Biology™   ONS/ONCC Chemotherapy Immunotherapy Certificate™   Safe Handling Basics   ONS Biomarker Database  ONS Learning Libraries:  Genomics and Precision Oncology  Oral Anticancer Medication   To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an Oncology Nursing Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From This Episode  “It was discovered that when you have gene amplification of HER2, you get a resultant overexpression of that HER protein, and that overexpression leads to a driver for certain cancers. So, when you have an overexpression of HER2, it leads to the cancer being more aggressive. In fact, when we first started talking about HER2 positive breast cancer, the key thing is, if we look at just the disease, not disease and treatment, that the patients that have HER2-positive breast cancers, they tended to be more aggressive because you had those drivers.” TS 3:30  “Hertuzumab is also a naked antibody, but it binds to a different part of the extracellular domain. It prevents heterodimerization, so where trastuzumab prevents HER2/HER2, this presents HER2 and HER1, HER2 and HER3, HER2 and HER4 dimerization, and then that leads to downstream effects that causes cell arrest and leads to the benefit of inhibition.” TS 6:03  “Key thing here is that we've learned, is that sometimes, that drug, when it's released from the antibody, can be released from the cell and can hit cells around the cancer cell that overexpresses HER2. So that's called the innocent bystander effect. So we're learning a lot more about antibody–drug conjugates.” TS 7:35  “The tyrosine kinase inhibitors, they're interesting in that there are these small molecules, just like we know about other tyrosine kinase inhibitors that target intracellular catalytic kinase domain of HER2, so the internal part. Key thing is we have a number of different tyrosine kinase inhibitors and they target different parts of that family.” TS 7:54  “The infusion-related reactions are really interesting, because one of the things we do with infusion-related reactions is, if we're giving it in an IV formulation, we use those prolonged infusions for the first dose and then go faster with subsequent doses after we see how they tolerate. And then of course there is the development of these onc products that are given sub-Q that have less of the infusion-related reaction.” TS 15:49  “One of the things that I see, I hear, is people say about these antibody–drug conjugates, which, you know, we use in all different diseases now. I hear so many people say these are not chemotherapy, and the thing of it is, they're chemotherapy. I think people like to say they're not chemotherapy because it makes people feel better that they're not getting chemotherapy. But the reality of it is, is that they are monoclonal antibodies linked to a chemotherapy. So some of the side effects that you get are related to the chemotherapy. I think people need to realize that. You need to know what you're giving.” TS 18:31 

The European Society of Medical Oncology Congress has begun, and Michael and Josh are on the ground, bringing you breaking studies and heartbreaks along with some important updates in the science and art of medical oncology.Michael and Josh cover a range of tumour types on day one, a slight deviation from our regular coverage. They look at hepatocellular carcinoma, renal cancers, and breast cancer, an eclectic but exciting mix of cancer types.Michael investigates HCC treatment with iparomlimab and tuvonaralimab with bevacizumab in a first line setting, along with some updated efficacy from the IMbrave050 trial. He finishes off his whirlwind tour of day one summarising some interesting education points in the metastatic colorectal cancer space. Josh looks at Tivozanib-Nivolumab in advanced RCC following immunotherapy, along with another trial where Belzutifan may be another treatment option. He finishes up with HER3-directed therapy!Links to studies discussed in this episode (subscription may be required):Phs II/III DUBHE-H-308Imbrave050 (HCC)TiNivo-2 Study (mRCC)Litespark 005 (mRCC)Checkmate 8HW (mCRC)Icarus-Breast 01 (mBreast Cancer)For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comSpotify Link to Prof Joshua's podcast, Dangerous Ideas in Drug Development: https://podcasters.spotify.com/pod/show/nectaOncology for the Inquisitive Mind is recorded with the support of education grants from Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have no editorial rights or early previews, and they have access to the episode at the same time you do.Art courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

CME credits: 0.50 Valid until: 13-09-2025 Claim your CME credit at https://reachmd.com/programs/cme/targeting-resistance-in-egfrm-nsclc-with-her3-directed-adcs-in-the-community-setting/24489/ The treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC) that has progressed on EGFR TKI therapy remains a clinical challenge, as traditional therapies have yielded only modest results. However, recent findings show that targeting HER3 can produce dramatically improved clinical outcomes. Data are rapidly emerging from late-phase trials evaluating HER3-directed antibody-drug conjugate therapies, and it is thus crucial for community-based oncologists and interprofessional care team members to be aware of these findings so they can be prepared to integrate these therapies into practice once they are available. In this activity, expert faculty in the field of NSCLC will evaluate recent data supporting the use of HER3-directed ADCs in the treatment of locally advanced and metastatic EGFR-mutated NSCLC that has progressed on EGFR TKI therapy, optimal management strategies for treatment-emergent adverse events related to these therapies, and the potential role of these agents in the current treatment paradigm. Faculty will also discuss best practices for a successful multidisciplinary approach and for optimized shared decision-making with the patient. Finally, case discussions will conclude the program to reinforce key learnings from the didactic section of the activity. =

CME credits: 0.50 Valid until: 07-03-2025 Claim your CME credit at https://reachmd.com/programs/cme/unlocking-the-potential-of-her3-targeted-therapy-breakthroughs-in-egfr-mutant-nsclc-therapeutic-approaches/16214/ Dive into the forefront of precision oncology with Drs. Pasi Janne and Jyoti Patel, where they unravel the potential of HER3-directed antibody-drug conjugates (ADCs) in revolutionizing treatment for NSCLC. Discover the transformative potential of HER3-directed ADCs in overcoming resistance to EGFR-targeted TKI therapies. This program offers a unique blend of trial results and practical strategies through the lens of a clinical case. Join us to lead the change in cancer care.=

Relatively new CEO Joseph Ferra has orchestrated some pretty significant change at Elevation Oncology in the two(ish) years since the Business of Biotech last hosted the company.  In that short time, Ferra advance from CFO to CEO, a move that aligned very closely with the company's difficult decision to shelve the late phase 2 anti-HER3 monoclonal antibody candidate it was founded on. Those big moves set the stage for Elevations' new lead candidate, a phase 1 Claudin18.2 target in the oh-so-hot ADC (antibody drug conjugate) space.  On this episode of the Business of Biotech, we go behind the scenes to learn why and how those daring moves were made, and how Elevation navigated the gauntlet of risk it assumed when it embraced disruption in a not-so-shiny biotech market. Subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!

In this episode our faculty take a look at the clinical trial data on HER3-directed therapies for breast and lung cancer. Visit www.morningcommutepodcast.com/HER3Agnostic2 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.

Our faculty continue their discussion about clinical trials of HER3-directed therapies with a look at treatment-related adverse events and how to manage them. Visit www.morningcommutepodcast.com/HER3Agnostic3 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.

In this episode, our faculty discuss the widespread expression of human epidermal growth factor receptor 3 (HER3) across tumor types and why clinicians should have HER3 on their radar. Visit www.morningcommutepodcast.com/HER3Agnostic1 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.

This first episode in a 3-part series tackles the role of HER3 in cancer, specifically in NSCLC, and how HER3 can be effectively targeted with ADCs.Presenters in this series include:Rebecca S. Heist, MD, MPHAssociate Professor of MedicineHarvard Medical SchoolMedical OncologyMassachusetts General HospitalBoston, MassachusettsHelena Yu, MDAssociate AttendingDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkSupported by an educational grant from Daiichi Sankyo, Inc. Link to full program, including a downloadable highlights slideset:https://bit.ly/48ecElW

This second episode in a 3-part series on HER3-targeted agents in NSCLC covers current clinical trials with HER3-targeted therapy, including:Recent data on patritumab deruxtecan (HER3-DXd) in the HERTHENA-Lung01 trialThe EGFRxHER3 bispecific antibodies BL-B01D1 and izalontamabThe HER2xHER3 bispecific antibody zenocutuzumabThe HER3-targeted antibody–drug conjugate SHR-A2009 Presenters in this series include:Rebecca S. Heist, MD, MPHAssociate Professor of MedicineHarvard Medical SchoolMedical OncologyMassachusetts General HospitalBoston, MassachusettsHelena Yu, MDAssociate AttendingDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkSupported by an educational grant from Daiichi Sankyo, Inc. Link to full program, including a downloadable highlights slideset: https://bit.ly/48ecElW

The third and final episode in a 3-part series covers the safety profile of and considerations for managing adverse events associated with HER3-targeted antibody–drug conjugates, including patritumab deruxtecan (HER3-DXd) and others, in the setting of lung cancer. Presenters in this series include:Rebecca S. Heist, MD, MPHAssociate Professor of MedicineHarvard Medical SchoolMedical OncologyMassachusetts General HospitalBoston, MassachusettsHelena Yu, MDAssociate AttendingDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkSupported by an educational grant from Daiichi Sankyo, Inc. Link to full program, including a downloadable highlights slideset:https://bit.ly/48ecElW

In this episode, Aakash Desai, MD; Narjust Florez, MD; and Paolo Tarantino, MD, discuss the biologic rationale and clinical development of agents targeting HER3 for the treatment of breast and lung cancers. The potential niche for HER3-targeted agents in these treatment landscapes is considered, with consideration of acquired resistance to previous targeted therapies and parallels to other approved antibody–drug conjugates. Their conversation covers clinical trial data from:Phase I/II study of patritumab deruxtecan in HR-positive/HER2-negative or triple-negative metastatic breast cancer, published by Krop and colleagues in the Journal of Clinical Oncology BRE-354: A phase II study of patritumab deruxtecan in several subtypes of previously treated advanced/metastatic breast cancer, presented at ASCO 2023ICARUS-Breast01: A phase II study of patritumab deruxtecan in patients with HR-positive/HER2-negative or HER2-low advanced breast cancer, presented at the ESMO Breast Cancer Congress 2023SOLTI-TOT-HER3: A window-of-opportunity study of neoadjuvant patritumab deruxtecan for treatment-naive HER2-negative early stage breast cancer, presented at the ESMO Breast Cancer Congress 2023HERTHENA-Lung01: A phase II study of patritumab deruxtecan in in patients with EGFR-mutated NSCLC after treatment with osimertinib and platinum-based chemotherapy, presented at the World Conference on Lung Cancer 2023HERTHENA-Lung02: An ongoing phase III study of patritumab deruxtecan vs platinum-based chemotherapy after osimertinib for the treatment of EGFR-mutated NSCLCeNRGy: A phase I/II study of the bispecific HER2 x HER3 antibody zenocutuzumab in multiple solid tumor types with NRG1 gene fusion, presented at ASCO 2022DESTINY-Breast04: A phase III study of trastuzumab deruxtecan for the treatment of patients with HER2-low metastatic breast cancer, published by Modi and colleagues in the New England Journal of MedicineDAISY: A phase II trial of  trastuzumab deruxtecan for the treatment of breast cancer with variable levels of HER2 expression including HER2-low and HER2-zero, published by Mosele and colleagues in Nature Medicine Presenters:Aakash Desai, MDAffiliation awaiting contractNarjust Florez, MDAssociate Director of The Cancer Care Equity ProgramThoracic Medical Oncologist, Dana-Farber Cancer InstituteAssistant Professor of Medicine, Harvard Medical SchoolBoston, MassachusettsPaolo Tarantino, MDAdvanced Research FellowBreast Oncology CenterDana-Farber Cancer InstituteBoston, MassachusettsContent based on an online CME program supported by an independent educational grant from Daiichi Sankyo, Inc.Link to full program: https://bit.ly/45UYsw3

In this JCO Article Insights episode, Davide Soldato interviews Dr. Jacob Sands, medical oncologist at Dana Farber Cancer Institute (Boston, MA) and Assistant Professor at Harvard Medical School, on their paper “First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01”. The interview offers a deep dive into the safety and efficacy data of this novel drug and puts these data in the context of the current treatment landscape of NSCLC and of the revolution that ADC are bringing into the oncology world. TRANSCRIPT Davide Soldato: Welcome to this JCO Article Insights episode for the October issue of Journal of Clinical Oncology. This is Davide Soldato, and today I will have the pleasure of interviewing Dr. Jacob Sands, co-author of the manuscript titled, “First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01.” Dr. Sands is a Medical Oncologist working at Dana-Farber Cancer Institute in Boston and Assistant Professor at Harvard Medical School. His main field of research and clinical interests revolve around improving screening and diagnosis of lung cancer and also on developing novel therapeutic agents for this disease.  So, welcome Dr. Sans, and thank you very much for accepting our invitation today.  Dr. Jacob Sands: Happy to join. Thanks for having me. Davide Soldato: I just wanted to start with a very general question because I think that we are going to discuss a very important study and the manuscript that you co-authored is going to look at the safety and the efficacy of this novel ADC datopotamab-deruxtecan that is targeting TROP2. But I just wanted to have a little bit of context before starting to discuss the safety and efficacy data. So the population that was included in the study included more or less 60% of patients that received three or more lines of therapy and also 20% of patients who received five or more lines of therapy. So I think that this is a very particular population, especially considering that we are speaking about non-small cell lung cancer. And so I wanted to get from you like a general context, like what are the therapeutic options for these patients normally in clinical practice and what do we expect in terms of outcomes and in terms of toxicity? Dr. Jacob Sands: Yeah, so as you point out, this is a highly pretreated population in general, which is to say that they've really gotten the most effective lines of treatment up to this point. Now, we certainly do see some efficacy from some of the later lines of therapies in some patients, but inherently there is a decreasing response rate and decreasing durability of these responses as patients get further along in their treatment courses as far as lines of therapy. So it's generally considered to be a challenging clinical scenario, which is part of what makes the data that we're going to discuss, I think, so meaningful.  Davide Soldato: Yeah, I think that especially if we look at the population that was included first, I think that the very particular thing is that included both oncogene-addicted and non-oncogenic addicted patients, and also the great majority of these patients received the most effective treatments that are available because they all received more or less immunotherapy and platinum-based chemotherapy, if I'm not mistaken. Dr. Jacob Sands: That's right. And that's an important distinction that you're drawing in the patients with oncogenic drivers and, of course, there's plenty of data with this compound with Dato-DXD in that population as well. But broadly speaking, in the non-oncogenic actionable alterations where they've gotten chemo-immunotherapy, those really are the most meaningful. Of course, docetaxel has been a long-standing second line that I'd say there is less and less enthusiasm about that as a line of treatment as we've seen some of these other more novel therapies that have just a better toxicity profile in particular, but also some with really durability that we don't quite see with docetaxel as well. And so once you're getting past that, you're really now reaching a bit deeper to then have something that is well tolerated and has efficacy. That's a setting where we really need it even more.  Davide Soldato: So, going back to the results of the study, as we kind of pointed out, this was a very standard classic with a Bayesian design, phase I dose escalation and dose expansion study of this novel ADC datopotamab-deruxtecan. So I just wanted to go over with you and to provide our listeners a little bit with some data regarding the doses that were explored and then what were the doses that were selected for the expansion. And also to discuss a little bit the safety data. We were discussing the tradeoff between risk and benefit, especially in patients that are very pretreated, searching for these kind of sweet spots between the toxicity and the efficacy. So I just wanted to put in context a little bit the data that you reported in the manuscript. Dr. Jacob Sands: Yeah, that's right. So, like phase I's go, we started with a low dose at 0.27 milligrams per kilogram, and dose escalations occurred up to 10 milligrams per kilogram. The 10 milligram per kilogram dose did have toxicities that really made it not considered to be tolerable, and that mostly being mucositis and skin. And so it was then back down to 8 milligrams per kilogram. And then there was a dose expansion at 4, 6, and 8 milligrams per kilogram. The 4 and 6 milligram per kilogram doses had 50 patients enrolled within those cohorts and 80 patients within the 8 milligram per kilogram cohort to then get much more data, of course, for efficacy and tolerability within those levels. Ultimately, each of them really demonstrated some efficacy as well as general tolerability. The 6 milligram per kilogram dose was really the one selected overall for further testing and future trials based upon the data out of this one that we're going to discuss further. Davide Soldato: What were the main side effects that you observed in the trial? And particularly, do you think that there is some kind of special toxicity that should be looked at when using this novel type of ADC? Dr. Jacob Sands: Certainly there are some novel toxicities to really pay attention to. And maybe I'll just point out before diving into the toxicities, that this is in many ways chemotherapy. The antibody drug conjugates, as listeners probably know, are an antibody that has a linker bound to chemotherapy, what's called the payload. And in this case, it's a topoisomerase I inhibitor with the antibody, the TROP2. So the cells on the surface, when there's TROP2 expression, the drug binds to that, gets pulled into the cell and releases that chemotherapy intracellular, but it is still chemotherapy. And so some of the toxicities are things that we commonly see with chemotherapy drugs. Although, broadly speaking, I would say we're able to deliver higher doses of that chemo to the cells in this kind of targeted dosing of chemotherapy to give the chemo intracellular.   Now, that being said, some of the toxicities that we see from this drug in particular that are a bit different is the stomatitis, mucositis. That is something that has occurred. Now, I've found that if it's really severe, then with a dose reduction that has really substantially improved any toxicities with future dosing. And at a 6 milligram per kilogram dose, a dose reduction to 4 milligram per kilogram is still within a dose range where we saw plenty of efficacy within the trial that we're discussing. That being said, if one can help patients tolerate it better, if it's more mild symptoms, if it's not severe, then that's better in maintaining that dose. And interesting things like ice chips at the time of infusion, so cold within the mouth, kind of like the cold caps to try to reduce alopecia at the time of infusion of the chemo may help some steroid rinses also can be helpful. But really these are things to help prevent stomatitis from being severe. It's harder when that occurs, then the treatment for improving it is a bit different.   We do know, though, that that does improve with time. So even when it was severe with that infusion, it does improve as patients get further out from those doses. Of course, another one is dry eyes or irritation within the eyes. And if that is severe, then or even mild actually, I'd say when there's any known toxicity like this is to involve ophthalmology. Now, within this trial, ophthalmology was involved and patients had to get a baseline eye exam and they would get checked at different time points throughout the course of the trial. And so they were being monitored. I did not have anyone who needed to stop the drug because of this. The patient I had with the longest standing response to therapy did have some dry eye. It was not bothering him so much. And he had this real aversion to using eyedrops. It was very hard for him to make himself use these. But when I told him, “Look, if this gets worse, you might have to come off the trial, that it might not be our decision just by the way the trial describes it, if this gets worse.” And so for him, the fear of having to come off the drug was really the thing that helped him to then start using his eyedrops, which really helped to control that a bit more. And so that is something to monitor for.  But the biggest thing really is interstitial lung disease. This is something that is a complex topic, I think because it's something that we need to be very aware of and monitor for. At the same time, a diagnosis of interstitial lung disease can be challenging. There really were not cases where we had pathologic confirmation of this diagnosis. These are clinical diagnoses in the cases on this. Now there was an adjudication committee that would review all of the data and come to a determination of whether this looked like drug related ILD or not. But for clinicians, when you see a patient whose scan shows some inflammatory markings or inflammatory appearing markings on a scan, we see that all the time with other drugs too. And so determining what is potentially incidental versus drug related, I think in most cases on a trial when we're unsure, we lean toward drug related. And in some cases there are reported out severe cases of drug related ILD.  I think the really difficult thing that I'd want people to take away from all of this, though, the bottom line is, yes, we need to be very aware of the potential for drug related ILD while at the same time, we need to not reflex, just call things drug related ILD and really make sure that we're doing a workup when feasible rather than just that bottom line conclusion. We see it at a rate related to the drug, and I do think it's real. But we also need to, when treating individuals, try to identify any other potential etiology. I did have one patient that really looked absolutely classic for this diffuse drug related ILD that ended up ultimately really being what looked more like tumor progression in just a radiographic pattern that looked more like an inflammatory process than it did the way we would typically see cancer progression. And so this has really, for me, I think, highlighted this as a topic where I'm diving a bit more into that description.  Davide Soldato: And I also think that in the population of lung cancer patients, as you were saying, this is even more complicated because frequently these are patients who had a history of smoking, who can have concomitant infections where progression is easier in the lung. If I think, for example, other ADC that have already been tested, for example, in breast cancer, it might be far easier to detect and to adjudicate an ILD to the drug that we are using compared to what could be, for example, for lung cancer patients.  So if I understood correctly, the toxicity that in your opinion as a clinician, they are more complicated to treat, let's say on a more daily basis, are more stomatitis and inflammation, but maybe the one that you experience as potentially more severe are always related to lung toxicity.  Dr. Jacob Sands: Well, I think the scary thing about the ILD is that we have higher grades of ILD, and this is a toxicity that then can become life threatening. When we see a grade I or a grade II ILD reported in numbers, where we see, okay, this looks like it's really happening, and then see some really higher grade toxicities, I think the concern amongst clinicians then is if they're seeing lower grade, which of those can potentially progress to those higher grade, which then becomes life threatening toxicities. Whereas dry eyes certainly can become a nuisance, we didn't see any blindness or something like this, and the stomatitis resolves as you hold the drug, and in some cases, really before the next cycle even comes, it's just more a matter of controlling the discomfort, which can be severe. I'm not minimizing that. I think that's why ILD stands out so much, is that that becomes a potentially life threatening thing.  And to your point exactly, these patients with a smoking history on other drugs, we see these inflammatory findings. Now, in some cases, we know it can be from the drug. In other cases, we see it and know that it's essentially incidental. And I'll say to patients, “Hey, we see this. It's something we'll monitor on future scans, and these can wax and wane.” When you have a patient on a drug with a high attention towards something like ILD, there can be- what I'm cautioning against is a reflex attribution to that drug. In all cases. I'd urge clinicians to individually assess each of these patients to get a sense of whether they think that that's going on for that person, knowing that it's often not possible to say with 100% certainty in any of these cases. But we often see waxing and waning inflammatory findings. And in many of these patients with heavier smoking histories, in particular, there can be waxing and waning respiratory symptoms. So the question is, are there instances where there is what really is an incidental inflammatory findings and incidental respiratory waxing and waning that then suddenly we call a grade II?  At the same time on the other part of that, if there is something that seems like it really may be drug related ILD, is doing that work up and really evaluating and diagnosing that before it progresses to a point that really there are severe symptoms. And it's kind of trying to do both of those things on the opposite ends of the spectrum that I'm speaking toward at the same time. Davide Soldato: Just on a personal note, do you think that, as we continue the development of these drugs that are associated potentially with lung toxicity, do you think that we also need to pay attention to the drugs that were immediately previously received by the patients? What I mean is, do you have the feeling that the previous treatment could potentially impact on the risk of developing this type of toxicity in the lung? Dr. Jacob Sands: I don't know that we yet have data to draw any real conclusions around that. But you raise an important question within this, and what potential toxicities could be related to prior treatments or synergy across those. Of course, we see inflammatory findings within the lungs and pneumonitis with prior immune-related therapies, and that it would be a good prompt to the question you're asking. And that in particular, we also see this in some of the targeted treatments, although not nearly to the same percentages. I don't know that we can draw conclusions from this. I would speculate that the mechanisms of action of each of these drugs are so different that I would not hypothesize real synergy in those toxicities. But it is certainly something to be aware of and an important question that you're raising. Davide Soldato: I think that, apart from the safety data that I think we dissected, the other end of the spectrum would be finding a drug that this very pre-treated population could still give us some efficacy data. So you already mentioned that, in the dose expansion cohorts, so 4, 6, and 8 milligrams, we had more or less signals of activity and of efficacy of these novel drugs. So the therapeutic options, as you were mentioning, are potentially docetaxel or other types of mono chemotherapy. But we know that the objective response rate is not that high, and that progression-free survival is not that long with these types of drugs. And potentially the safety profile could also be complicated in patients that are also pre-treated. So I just wanted to discuss a little bit the efficacy data and to see if there is really promise in this type of delivery of chemotherapy as you were saying with the ADC. Dr. Jacob Sands: We saw response rates of about 25% across all three of those cohorts. The manuscript outlines the 4, 6, and 8 milligram cohorts within a chart showing the efficacy outcomes. And really it's around 25% across the three of those, which in this patient population, as we've discussed, heavily pre-treated, to have a response rate of 25% is really quite promising that there really is a substantial treatment effect. On top of that, we also see a duration of response of really around 10 months. So, in the patients that are having a response, there really is some durability. Now, it's tragic that 10 months is considered durable within this population and it really highlights the ongoing need for further drug development because I don't think anyone would say that 10 months is enough, we need dramatically better. But within the context of what we currently have, a 10-month duration of response is really quite meaningful and a response rate of 25%.  Now, it also describes a disease control rate. And I always have to put a little asterisk to this. I think we see this increasingly - the disease control rate being reported - and it always looks quite a bit better than the response rate. And that's essentially incorporating stable disease. And although I would never claim that everybody with stable disease is truly benefiting from a drug, across all of the studies where this is reported out, there is a spider plot which really highlights a number of patients that are not considered responders, but with responses, a handful of them beyond six months of disease control, even though they're not considered responders, and one of them beyond a year with still ongoing disease control. So, even within that stable disease group, I'd say there are some who are really clinically benefiting from the drug, which is to say that really, even beyond the 25% response rate, we are seeing some others that are truly benefiting from this.  Davide Soldato: Yes, and I also think that for these patients, especially when they can develop very rapidly symptoms that can potentially also impact quality of life, having a drug that achieves this level of stability - with maybe no deterioration in clinical symptoms - I think that it's still probably a very meaningful objective to obtain for this type of population. Of course, I think that with future studies we will also have probably health-related quality of life data that will tell us more about the impact of this type of drug in this setting. But I still think that this could be potentially a relevant endpoint, even if we don't achieve what we officially consider as a response as per resistor criteria.  So I think that we have talked a little bit about the efficacy data. So, we are kind of entering a novel area where more and more ADCs are being tested, are being included in clinical practice. For example, if I think about breast cancer, we already have two that are approved that can be used, the same in bladder cancer. So, as you participated in this phase one trial, I just wanted to have your opinion: if you think that, in the future, we are going to evolve completely towards this type of delivery of chemotherapy, using what we call now "smart drugs" in terms of delivery of these cytotoxic agents. Dr. Jacob Sands: It'll be interesting to see. We certainly will see other generations of ADCs. I mean, I think we're really just at the beginning with this technology. We certainly have now a very solid foundation to build upon, where we have effective targets and effective payloads. We've highlighted some of the toxicities we're seeing from that. Also, I'd highlight within this drug with TROP2, the amount of expression has not seemed to really be a driver in this. And some of that may be the bystander effect, which I'd call a real benefit of the drug, where the payload as a drug goes through apoptosis and lysis, that payload that releases then into the surrounding- toward the surrounding cells is membrane permeable and crosses into other cells, leading to potentially more efficacy. That technology in itself, I'd say, is something that we may see incorporated further into next generations of ADCs. Whether there can be improvements in preventing toxic drug in other sites like the stomatitis, for example, with newer generations that evolve from this, we'll see.  I don't know that I would anticipate all chemotherapy ultimately going through ADC technology, but I certainly believe that this is the beginning of what I would call a whole new class. But would future cytotoxic treatment happen more so through ADC than just broad circulating payloads? If we can call it that. And I certainly think we'll see a lot more development like that. But you know, we may see other ways of developing the cytotoxic drugs in other forms of delivery as well. It'll be exciting to see as we go forward. Davide Soldato: I also think that one of the major challenges that we probably will have to deal with, in probably not so long, is also the sequencing of these types of agents. We are starting to have, as I was saying, accumulating data regarding the efficacy of these drugs. And some of them share either the same payload or they target the same antigen on the cell. And so, do you think that we will need as a new line of research to really go into the field of cross resistance when we are using and trying to sequence these types of novel agents?  Dr. Jacob Sands: We're seeing that across various tumor types. I mean, to stick with lung in particular and small cell lung cancer, we've seen DLL 3 really be a demonstrated target for small cell lung cancer. And now we have a handful of drugs being developed that target DLL 3. How would we potentially utilize those drugs? In what orders and which ones over others is going to be an area for discussion, much like the area you're raising here, where we see TROP2 directed treatments. And so which one would you choose? On top of the fact that there are other targets, in this case, we're talking about TROP2, but of course, there's HER3 that we've seen, and especially when we're talking about an EGFR population, EGFR mutation population, we've seen good efficacy with this TROP2 antibody drug conjugate, as well as the HER3. And so how would we order those? And they both are using the same payload.   If we're talking about both of the deruxtecan compounds, this is going to take some sorting out. I think with time, it'll be tough. I don't know if we'll end up seeing head to head studies in this or if this is going to end up being shaped more by expert committees and their descriptions. But I imagine we'll see some heterogeneity in the treatment pathways at different centers just based upon preferences and familiarity with these different drugs. Of course, assuming that they all end up ultimately being approved and then that efficacy and tolerability that we're seeing continues to pan out in future trials. Davide Soldato: So we were mentioning before that there is a very big line of development for this novel ADC. And I think that there are also some trials that are exploring the role of data DXD so the datopotamab-deruxtecan in lines where patients have received less therapy or in combination with other agents. So I wanted to ask you if you could give us some insights regarding the ongoing trials, if you know about them. And also what do you think could be the area of a met need where this drug could potentially give the most effect? Dr. Jacob Sands: It'll be interesting to see. In the first line setting we have TROPION-Lung07 and TROPION-Lung08. These are studies with PDL-1 expression of less than 50% or greater than or equal to 50%, the greater than equal to 50% being plus pembrolizumab versus pembrolizumab alone. The less than 50% essentially being an incorporation with or instead of chemotherapy along with the platinum-based therapy plus pembro. And so that one is a more complicated three-arm study. Now, essentially what this is looking at is incorporating this antibody drug conjugate in place of chemotherapy for potential tolerability when given concurrently with the platinum and pembro. Whether or not we'll see some synergy with the chemo and the pembro, I guess I would hypothesize that we would likely see at least similar to when giving the chemotherapy, or at least that's the hypothesis driving the trial design.   If anything, whether we note improved tolerability relative to those getting, I'd say the carboplatin component, because certainly within non-squamous, non-small cell, pemetrexed is generally very well tolerated. And so that's a bit tougher to beat out from a toxicity standpoint. The trials are really designed based upon the efficacy that we've seen from this trial you're pointing out. I think by the time that this podcast is heard, we'll have the data from TROPION-Lung01 that'll be reported out as well in the second line setting versus docetaxel as that data is near release. These are areas for ongoing attention, certainly. Davide Soldato: Thank you, Dr. Sands, for being with us today. This concludes our episode of JCO Article Insights. We discussed with Dr. Sands the results of the manuscript titled, “First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01.”  This is Davide Soldato. Thank you for your attention and stay tuned for the next episode. 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.  

Dr. Omkar Desai, from the Department of Surgery at Case Western Reserve University and University Hospitals Cleveland Medical Center, describes a research perspective he co-authored with Dr. Rui Wang that was published by Oncotarget in Volume 14, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.” DOI - https://doi.org/10.18632/oncotarget.28421 Correspondence to - Rui Wang - rxw517@case.edu Author video - https://www.youtube.com/watch?v=3-02jt7-MW8 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28421 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironment About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/YMP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Antibody–drug conjugates (ADCs) are the next frontier in the treatment of lung cancer, addressing unmet needs, expanding options, and providing new hope of improved outcomes for diverse populations of patients. Extensive efforts are ongoing to evaluate and bring new ADCs to clinical practice, including those targeting HER3 and TROP2. Initial studies have already yielded promising new data, and many other clinical trials are actively evaluating ADCs targeting HER3, TROP2, and others in different patient populations and treatment settings. This educational activity, based on a recent live symposium, provides an expert-led exploration of the fast-paced evolution of the role and impact of ADC-based approaches in lung cancer. Learners can achieve a better understanding of the structure and function of modern ADCs, the rationale for targeting HER3 and TROP2 with ADCs in lung cancer, and the rapidly accumulating evidence base supporting their use in practice. Going beyond the basics, the expert panel also shares in-depth perspectives on where the novel ADCs may fit within the complex lung cancer treatment arsenal, nuances of patient selection, how to best integrate them into treatment plans, and how to recognize and manage unique adverse events associated with different ADCs. Watch this activity to learn how to maximize the potential of these novel ADCs for the benefit of patients with lung cancer. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting HER3 and TROP2 with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and safety and efficacy profiles of ADCs targeting HER3 and TROP2 in NSCLC; Identify patients with NSCLC who are likely to be appropriate candidates for treatment with novel ADCs targeting HER3 and TROP2; and Implement best practices to effectively and safely integrate novel ADCs, including those targeting HER3 and TROP2, into treatment plans for appropriate patients with NSCLC

An experimental drug for EGFRm NSCLC, patritumab deruxtecan (HER3-DXd), raises some eyebrows and a new agent is FDA-approved for hematopoietic stem cell mobilization (motixafortide).

Dr. Shannon Westin and her guest, Dr. Helena Yu discuss the paper "HERTHENA-Lung01, a Phase 2 Trial of Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI Therapy and Platinum-Based Chemotherapy" published in the JCO during the World Conference on Lung Cancer in Singapore.  TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in-depth on manuscripts that are published in the Journal of Clinical Oncology. I am your host, Dr. Shannon Westin, GYN Oncologist and Social Media Editor of the JCO. And as always, it's my pleasure to review an incredibly exciting manuscript.  Today, we're going to be talking about “HERTHENA-Lung01: A Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in EGFR-mutated NSCLC Following EGFR TKI Therapy and Platinum-based Chemotherapy.” And this is exciting. This is a simultaneous publication in the JCO on September 10th, 2023 at the same time it's being presented at the World Conference on Lung Cancer in Singapore.  I am joined today by the first author and overall outstanding physician, Helena Yu. She's an Associate Attending Physician, Thoracic Oncologist, and Early Drug Development Specialist at Memorial Sloan Kettering Cancer Center in New York, New York.  Welcome, Dr. Yu.  Dr. Helena Yu: Thank you. I'm glad to be here, and thanks for having me.  Dr. Shannon Westin: So we're so excited to have you, and we love doing these simultaneous podcasts because I think not everyone can go to Singapore and be with you today. So it's awesome that we'll be able to give people the data that they want to see as soon as possible.  So first, let's just level set. Coming from the GYN Oncology standpoint, I always like to get down to the basics of the cancer. So, can you speak just a little bit about the incidence and mortality of lung cancer overall and what have been some recent trends in the treatment of this disease?  Dr. Helena Yu: Everyone knows somebody that has been touched by lung cancer. It's the second most common cancer that is diagnosed in men and women in the US today. It is the leading cause of cancer-related deaths, with 25% of cancer deaths really being attributable to lung cancer. Historically, prognosis with lung cancer has been poor, with five-year survivals around 10%. What's really interesting is over the last couple of years, there have been some improvements in survival with lung cancer. And I think that that can largely be attributed to the advent of immunotherapies as standard of care, as well as targeted therapies for driver mutation-positive lung cancer.  Dr. Shannon Westin: So that leads right into the next question: What is the role of the EGFR pathway in lung cancer? How common are these aberrations and how successful have prior treatments targeting this pathway been?  Dr. Helena Yu: Yes. So we, in lung cancer, have this mutation pie, which really describes the different oncogenes that we see in lung cancer. And probably now two-thirds of patients actually have a detectable driver mutation when their tumors undergo next generation sequencing. EGFR is probably one of the first mutations that was identified. About 15% to 20% of patients diagnosed with lung cancer in the US have mutations in EGFR. It is both activating and sensitizing. So, obviously mutations in EGFR cause cancer and they are sensitizing to different EGFR targeted therapies we have.   Right now, the standard of care for first-line treatment for EGFR mutant lung cancer are EGFR tyrosine kinase inhibitors. And those are oral therapies that actually are very successful at managing EGFR mutant lung cancer. They're not curative, but they do kind of control disease for a long period of time. But unfortunately for all patients, at some point their cancer does progress on these targeted therapies. And the most common one we use today is one called osimertinib, which is a third-generation EGFR TKI. And we do not have any approved targeted therapies after osimertinib. And so that kind of is the setting for this new drug, patritumab-deruxtecan.  Dr. Shannon Westin: So tell us a little bit about HER3-DXd and why you prioritize targeting this particular part of the EGFR pathway in this population.  Dr. Helena Yu: Yes. So HER3 is actually part of the HER EGFR family, and it is a protein that, when expressed, really portends a poor prognosis. It kind of tells us cancers that are more likely to recur and cancers where overall survival is shorter. So HER3-DXd is an antibody drug conjugate. There are a slew of new medicines in lung cancer that are ADCs. Historically, we looked at HER3 monoclonal antibodies in EGFR mutant lung cancer and they actually were not successful, not efficacious. And so it's really interesting that using these antibodies as part of an ADC construct has led to better efficacy.  The HER3-DXd has that HER3 monoclonal antibody, there is a linker and then there is a chemotherapy payload. So for the deruxtecan family of which there are a few ADCs has a topoisomerase 1 chemotherapy, and in part, we know that HER3 is sort of more significantly expressed in these EGFR mutant lung cancers. And because HER3 is part of the EGFR family and heterodimerizes with EGFR, it was sort of a natural initial population to study this drug.  Dr. Shannon Westin: Why don't you briefly highlight the design of the trial and your key eligibility for our listeners? Dr. Helena Yu: So this phase II study came off the heels of an initial phase I study that helped us identify the appropriate dose of HER3-DXd for patients with EGFR mutant lung cancer. And so this study enrolled patients with metastatic EGFR mutant lung cancer. All patients had to have received EGFR TKI, most of them received osimertinib and that's first line standard of care globally. And then also patients had to receive platinum doublet chemotherapy, which is really our second line standard of care treatment. The initial study randomized patients to two cohorts. One, which was all patients received 5.6 milligrams per kilogram every three weeks intravenous. The other cohort was an uptitration cohort, where they actually started with lower doses and then kind of sequentially over cycles increased the dose to see if that mitigated toxicity based on emerging phase I data that really showed that the 5.6 milligram per kilogram had the better efficacy as well as better toxicity profile. Pretty soon after the study started, all patients received that 5.6 mg per kilogram.  And I think the other important thing to say is that patients with asymptomatic brain metastases were allowed. Lung cancer, in general, has a very high incidence or frequency of brain metastases. But in EGFR mutant lung cancer that number is north of 50%. So having a therapy that is effective in the CNS is especially important for this population. Dr. Shannon Westin: So let's talk a little bit more about this population. The group that you enrolled and treated, is it representative of the general population that we might see in the community?  Dr. Helena Yu: Yes, I think so. I think that one thing to highlight are these patients were pretty heavily pretreated. The median prior lines of therapy were three lines prior to study enrollment, but I think that went up to eleven for certain patients. And so that is one thing that I think is unique about this population, where they're able to sort of receive several sequential therapies. I think it was unique in allowing those asymptomatic brain metastases and then EGFR mutant lung cancer has certain demographic tendencies. And so we see women, Asian, never smokers, which may not kind of represent the typical demographic for lung cancer, but certainly is the typical demographic for EGFR mutant lung cancer. Dr. Shannon Westin: Got it. And let's hear about your primary results. What did you discover? Dr. Helena Yu: To set the stage, this is really an unmet need where post EGFR TKI and post chemotherapy, we really don't have exciting efficacious therapies. When you look at real world studies, the response rate to third line and beyond treatments are less than 10% PFS less than three months. And so really searching for something in this treatment landscape. And so for the study, the primary endpoint was confirmed overall response which was 30% for this patient population. Duration of response was 7.4 months and the median progression free survival was 5.5 months. Looking at sort of prespecified subgroups, there really did not seem to be a particular subgroup that had enhanced benefit.  Dr. Shannon Westin: So that is a really impressive improvement in the expected standard of care results. So I congratulate you and I'm so excited.  I was also really excited to see that you included patients with the asymptomatic brain meds for the recent ASCO-Friends guidelines. Can you speak a little bit about the efficacy in this population specifically? Dr. Helena Yu: Absolutely. As I mentioned before, for these novel targeted therapies, we really do need to look specifically at CNS efficacy because that is absolutely an area where we often see disease progression. And so having studies that allow those patients really is more representative, of course, of the clinical practice that we actually treat. And so when you look at the subgroup that had a history of brain metastases, which in this group was actually, I believe, 51%, so the majority of patients, the response rate was really similar to the patients that did not have brain metastases. I believe it was 29% response rate for patients with brain metastases and 30% for patients without.  And I think what is especially useful that we did was we had specific neuroradiologist look for measurable target lesions within the CNS that had not received prior radiation or prior local therapy to look at intracranial response rate. And so there were a subgroup of patients, 30 patients that had measurable target lesions within the CNS and the confirmed intracranial response rate was 33.3% in those patients with measurable target lesions in the CNS and disease control rate was 77%. So, I think, it's really exciting to see that the response rate in the CNS was really comparable to what we see with systemic disease. Dr. Shannon Westin: That is awesome. I don't think I've ever seen anything quite like that. So really, you and your co-authors are to be congratulated for including this really important population.  I guess the next natural question is, how was HER3 expression? Did you look at that? How was it associated with response to therapy? And did you find any other intriguing genomic alterations associated with benefit from the HER3-DXd?  Dr. Helena Yu: That is a super interesting topic because I think in lung cancer we are well familiar with these driver mutations that really are the biomarker for targeted therapy. It is less clear what the appropriate biomarkers are for some of these antibody drug conjugates. We absolutely looked at HER3 expression, pretreatment tissue was required for this point specifically. And actually within EGFR mutant lung cancer, almost all patients have some degree of HER3 expression. And so we're already looking at a population that is enriched for potential response.  But we actually looked at H-scores, looking at membrane HER3 expression and really did not find differences in the degree of HER3 expression when you compare patients with response versus stable disease versus progressive disease. So I don't think the degree of HER3 expression really is an appropriate biomarker. And I think we're still figuring out with ADCs, I think you actually might need very little of the surface protein for these ADCs to be internalized and be effective. So, right now, the disease population of interest is EGFR mutant lung cancer, where we think there's reasonable efficacy. Dr. Shannon Westin: And that makes sense. And with this particular drug, is there a bit of bystander effect as well, like we've seen with some of the other ADCs?  Dr. Helena Yu: There absolutely is a little bit. And I think what is interesting for this drug too is there are a few ADCs that are in development. So there is trastuzumab-deruxtecan, which is already approved for HER2 positive lung cancer; and then there is also datopotamab-deruxtecan, which is a TROP2 ADC. And so I think there really will be a wave of these different ADCs which are studied in slightly different populations. But I think understanding what the biomarker is for these and then, will there be cross resistance because of the similar chemo backbone, is something that we will need to find out in the future.  Dr. Shannon Westin: Yeah, these are definitely unmet needs in this space.   I guess one other question just around safety signals, anything unique for this particular agent? Kind of take us through the dose interruptions and dose reductions?  Dr. Helena Yu: Absolutely. So I think that it is important to remember, and I do remind all of my patients that have consented to this study, that ADCs are a hybrid chemotherapy agent. So they will have some of the typical chemotherapy adverse events like cytopenias. We did see a little bit of alopecia with this as well. So I think there's thrombocytopenia and neutropenia that actually is more front-loaded and actually weren't necessarily associated with significant clinical sequelae like bleeding or neutropenic fever.  The rate of treatment discontinuation from adverse events was actually pretty low at 7%; but about 20% of patients did require a dose reduction, and many of the side effects do appear to be dose-dependent. So I think those dose reductions are helpful. And then a really important side effect of this class of drugs is ILD or interstitial lung disease or pneumonitis. And we've seen kind of varying ranges of pneumonitis with these drugs. So far it really looks to be the highest with trastuzumab-deruxtecan with an ILD rate north of 15%; but with this drug, the independently adjudicated rate of ILD was 5%. So present, but maybe not as high as some of the other drugs in this class.   Dr. Shannon Westin: Well, that's great news. Well, congratulations on these exciting results and your presentation and your paper.  The last question I have for you is what's next for this agent? What do you see? Where do you see it going? Dr. Helena Yu: Absolutely. So I hope that with these promising results in an area of unmet need, that we will get approval for this drug so that we can get access to our patients. The other interesting thing that we are looking at is combining HER3-DXd with osimertinib, which is the standard of care EGFR inhibitor. So the idea of combining this novel therapy with the standard targeted therapy for this type of cancer, I think, is really interesting to see if we'll get even sort of greater efficacy and in particular greater CNS efficacy by combining two CNS active agents. So those are results that I'm looking forward to seeing, too. Dr. Shannon Westin: That's great. Well, thank you so much for being here, Dr. Yu. And congratulations again on these incredible results and your incredible success in the lung cancer space.   And thank you all of you for listening in to JCO After Hours, again, discussing the “HERTHENA-Lung01: Phase II Trial of of HER3-DXd in EGFR Mutated Non-Squamous Cell Lung Cancer.” We are always excited to have you. Please check out our other podcasts, reach out and let us know how we did. And until then, we'll see you next time.   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.      

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Go online to PeerView.com/YEN860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Mounting evidence continues to elucidate the clinical potential of antibody–drug conjugates (ADCs) in the treatment of patients with lung cancer. ADCs are now transitioning from research settings to clinical practice, with the first approval of a novel HER2-targeting ADC, trastuzumab deruxtecan, for HER2-mutated NSCLC. In addition, various other potent ADCs targeting HER3, TROP2, CEACAM5, c-MET, AXL, ROR2, and others are being evaluated in clinical trials in different disease settings, including in patients with advanced NSCLC with and without actionable genomic alterations, and they are showing impressive activity. How do we realize the promise of these ADCs as the next frontier in precision lung cancer care? What are the best ways to apply the emerging science to patient care decisions in everyday practice? These and other key questions are addressed in this activity, which is based on a recent live symposium and produced in collaboration with the LUNGevity Foundation to highlight patient perspectives alongside those of clinicians. Leading experts in the field share their interpretations of the latest practice-changing evidence and provide practical guidance using real-world case scenarios to demonstrate how to maximize beneficial patient outcomes using ADCs. Upon completion of this activity, participants should be better able to: Discuss the modern composition, rationale for use, and clinical potential of novel ADCs in NSCLC; Compare the characteristics, efficacy/safety, and ongoing investigations of novel ADCs in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for targeted therapies, including novel ADCs; and Utilize best practices for identifying and managing treatment-related adverse events in patients receiving targeted therapies for NSCLC to promote optimal adherence, outcomes, and quality of life

Javier Cortés, MD, PhD - Updates on HER3-Targeted Therapies in NSCLC and Breast Cancer

Javier Cortés, MD, PhD - Updates on HER3-Targeted Therapies in NSCLC and Breast Cancer

Javier Cortés, MD, PhD - Updates on HER3-Targeted Therapies in NSCLC and Breast Cancer

Javier Cortés, MD, PhD - Updates on HER3-Targeted Therapies in NSCLC and Breast Cancer

Cancer is facing a seismic shift as precision oncology is becoming a reality, and adoption is skyrocketing as new anti-cancer agents are released. It appears that the days of blunt-force chemotherapy could be limited. Paul Ehrlich, the German Chemist, is credited with the term "chemotherapy", but more importantly, the concept of the magic bullet, "zauberkugel", which would allow selective targeting of pathogenic microbes without affecting other parts of the body. Leading the field of targeting cancer is metastatic breast cancer, as demonstrated by ASCO23. Oncology for the inquisitive Mind explores CDK4/6 sequencing, antibody-drug conjugates, and HER3 targeted therapy. Michael and Josh dissect the SONIA trial, sacituzumab govitecan use in the hormone receptor-positive space and partritumab deruxtecan, which could have pan-breast cancer utility.StudiesSONIA: https://meetings.asco.org/abstracts-presentations/219701TROPICS-02: https://meetings.asco.org/abstracts-presentations/219698PARTRITUMAB DERUXTECAN: https://meetings.asco.org/abstracts-presentations/219699Many thanks to Merck for supporting this episode. Merck provided virtual access to ASCO 2023 but did not review or approve any part of OftiM's coverage of ASCO.For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

A new research perspective was published in Oncotarget's Volume 14 on May 10, 2023, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.” Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are highly metastatic cancers with poor survival rates. The tumor microenvironment has been shown to play a critical role in cancer progression and response to therapies. Endothelial cells (ECs) are a key component of the tumor microenvironment and promote cancer cell survival by secreting soluble factors that activate cancer-promoting signaling pathways. In this new perspective, researchers Omkar Desai and Rui Wang from Case Western Reserve University and University Hospitals Cleveland Medical Center discuss their studies and others that have identified HER3 as a key mediator of liver EC-induced chemoresistance and cancer cell growth in metastatic CRC and PDAC. “In complement to our studies, prior preclinical studies have shown that HER3-targeted therapies with antibodies and inhibitors have been effective in blocking tumor growth in several types of cancers [22, 23], specifically breast cancer [24], head and neck squamous cell carcinoma (HNSCC) [25], PDAC [25], and non-small cell lung cancer (NSCLC) [26]. However, translating the preclinical findings to clinical studies has shown limited impact on patient outcomes.” In this article, the researchers discuss that HER3-targeted therapies may be effective in treating patients with HER3-expressing CRC and PDAC, and highlight the importance of applying HER3 expression as a predictive biomarker for patient response to HER3-targeted therapies. They also discuss the challenges encountered in past clinical trials of HER3-targeted therapies, including the role of NRG1 gene fusions, alternative HER3 activation mechanisms, and adaptive resistance mechanisms. Finally, the team concludes by suggesting the future directions of HER3-targeted therapies, including novel approaches to overcome chemoresistance and promote cancer cell death. “In summary, we discovered that the surrounding liver EC microenvironment plays a key role in activating HER3 and promoting cell survival in mCRC and mPDAC, and potentially other types of cancer that metastasize to the liver.” DOI - https://doi.org/10.18632/oncotarget.28421 Correspondence to - Rui Wang - rxw517@case.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28421 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironment About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Julia Rotow, MD / Javier Cortés, MD - HER3-Targeted Therapies: How Might These Benefit Our Patients?

Go online to PeerView.com/PJD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. New, modern antibody–drug conjugates (ADCs) have emerged as promising additions to the treatment arsenal for patients with lung cancer, with the first HER2-targeting ADC recently gaining FDA approval for patients with unresectable or metastatic NSCLC whose tumors have HER2 mutations. Clinical trials are also underway with novel ADCs targeting HER3, TROP2, CEACAM5, and MET, among others, and have been yielding encouraging results to date. What are the unique structural and mechanistic features as well as efficacy and safety profiles of these ADCs? Where are they likely to best fit in the NSCLC treatment algorithms? What practical considerations should be taken into account when integrating these therapies into treatment plans? These and other topics are explored in this unique educational activity, based on a recent live symposium, in which experts compete to answer a series of challenge questions that frame explanatory evidence and panel discussions focused on the growing role and impact of ADCs in the treatment of NSCLC. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting of HER2, HER3, TROP2, and other alterations with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and latest safety and efficacy of ADCs targeting HER2, HER3, TROP2, and other alterations in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for novel ADCs and other targeted therapies; and Implement multidisciplinary and patient-centric approaches to effectively and safely integrate HER2-, HER3-, and TROP2-targeted and other novel ADCs into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/PJD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. New, modern antibody–drug conjugates (ADCs) have emerged as promising additions to the treatment arsenal for patients with lung cancer, with the first HER2-targeting ADC recently gaining FDA approval for patients with unresectable or metastatic NSCLC whose tumors have HER2 mutations. Clinical trials are also underway with novel ADCs targeting HER3, TROP2, CEACAM5, and MET, among others, and have been yielding encouraging results to date. What are the unique structural and mechanistic features as well as efficacy and safety profiles of these ADCs? Where are they likely to best fit in the NSCLC treatment algorithms? What practical considerations should be taken into account when integrating these therapies into treatment plans? These and other topics are explored in this unique educational activity, based on a recent live symposium, in which experts compete to answer a series of challenge questions that frame explanatory evidence and panel discussions focused on the growing role and impact of ADCs in the treatment of NSCLC. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting of HER2, HER3, TROP2, and other alterations with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and latest safety and efficacy of ADCs targeting HER2, HER3, TROP2, and other alterations in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for novel ADCs and other targeted therapies; and Implement multidisciplinary and patient-centric approaches to effectively and safely integrate HER2-, HER3-, and TROP2-targeted and other novel ADCs into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/PJD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. New, modern antibody–drug conjugates (ADCs) have emerged as promising additions to the treatment arsenal for patients with lung cancer, with the first HER2-targeting ADC recently gaining FDA approval for patients with unresectable or metastatic NSCLC whose tumors have HER2 mutations. Clinical trials are also underway with novel ADCs targeting HER3, TROP2, CEACAM5, and MET, among others, and have been yielding encouraging results to date. What are the unique structural and mechanistic features as well as efficacy and safety profiles of these ADCs? Where are they likely to best fit in the NSCLC treatment algorithms? What practical considerations should be taken into account when integrating these therapies into treatment plans? These and other topics are explored in this unique educational activity, based on a recent live symposium, in which experts compete to answer a series of challenge questions that frame explanatory evidence and panel discussions focused on the growing role and impact of ADCs in the treatment of NSCLC. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting of HER2, HER3, TROP2, and other alterations with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and latest safety and efficacy of ADCs targeting HER2, HER3, TROP2, and other alterations in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for novel ADCs and other targeted therapies; and Implement multidisciplinary and patient-centric approaches to effectively and safely integrate HER2-, HER3-, and TROP2-targeted and other novel ADCs into treatment plans for appropriate patients with NSCLC

Go online to PeerView.com/PJD860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. New, modern antibody–drug conjugates (ADCs) have emerged as promising additions to the treatment arsenal for patients with lung cancer, with the first HER2-targeting ADC recently gaining FDA approval for patients with unresectable or metastatic NSCLC whose tumors have HER2 mutations. Clinical trials are also underway with novel ADCs targeting HER3, TROP2, CEACAM5, and MET, among others, and have been yielding encouraging results to date. What are the unique structural and mechanistic features as well as efficacy and safety profiles of these ADCs? Where are they likely to best fit in the NSCLC treatment algorithms? What practical considerations should be taken into account when integrating these therapies into treatment plans? These and other topics are explored in this unique educational activity, based on a recent live symposium, in which experts compete to answer a series of challenge questions that frame explanatory evidence and panel discussions focused on the growing role and impact of ADCs in the treatment of NSCLC. Upon completion of this activity, participants should be better able to: Discuss the clinical importance and biologic rationale for targeting of HER2, HER3, TROP2, and other alterations with novel ADCs in lung cancer; Summarize the characteristics, mechanisms of action, and latest safety and efficacy of ADCs targeting HER2, HER3, TROP2, and other alterations in NSCLC; Apply the latest evidence and guidelines on patient assessment in NSCLC, including biomarker testing as indicated, to identify patients for novel ADCs and other targeted therapies; and Implement multidisciplinary and patient-centric approaches to effectively and safely integrate HER2-, HER3-, and TROP2-targeted and other novel ADCs into treatment plans for appropriate patients with NSCLC

Emerging Role of Antibody‑Drug Conjugates in the Management of Non‑Small Cell Lung Cancer — Faculty Presentation 1: Targeting HER2 and HER3 with Antibody-Drug Conjugates (ADCs) in Non-Small Cell Lung Cancer (NSCLC) — Dr Helena Yu CME information and select publications