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Medscape
11 hours ago
- Health
- Medscape
EGFR+ NSCLC: Experts Weigh Risk vs Reward at ASCO 2025
This transcript has been edited for clarity. Coral Olazagasti, MD: Hello. My name is Coral Olazagasti, and I'm a thoracic oncologist at Sylvester Comprehensive Cancer Center at the University of Miami. Joining me today is my friend and colleague, Maria Velez, a clinical instructor at UCLA, and also my other friend and colleague, Ana Velázquez Mañana, who's an assistant professor of medicine at UCSF. Today we are super excited because we are speaking about the ASCO 2025 Annual Meeting here in Chicago. We just came out from the oral abstracts for the metastatic setting for non-small cell lung cancer and we want to share some of the data that we learned. We want to start the discussion here today about EGFR -mutant disease in the second-line setting. We're going to start with Maria. Do you want to tell us a little bit about the HERTHENA-Lung02 study? Maria A. Velez, MD, MS: Sure. HERTHENA-Lung02 was a study that evaluated HER3-DXd, which is an antibody-drug conjugate (ADC), in the second-line setting for patients with previously treated EGFR -sensitizing mutations. It was an open-label study where patients received either the HER3-DXd or the investigator's choice chemotherapy, and the primary endpoint was median progression-free survival. The results showed that the median progression-free survival for patients who received HER3-DXd was 5.8 months whereas the median for the chemotherapy arm was 5.4 months. Even though it was a statistically significant difference, it was not a very clinically meaningful difference, with a huge implication that 100% of the patients in this study had treatment-related adverse events and some patients experienced interstitial lung disease (ILD). All in all, taking these data into account, even though there's a huge need in the treatment landscape for second-line EGFR -mutant patients, I think this ADC did not really show a substantial enough clinically meaningful benefit and had a large amount of toxicity. Olazagasti: Not to say that this study didn't show any overall survival (OS) benefit. We're talking about a drug that's not really giving patients a longer life and is also giving many side effects, like you mentioned — a large amount of discontinuation due to ILD, and so much toxicity without that benefit there. I think we'll table that regimen for now. Do you agree? Velez: I agree. Ana I. Velázquez Mañana, MD, MSc: I agree. Clearly, it's disappointing to see the results of not beating chemotherapy in the second-line setting, but I do think that potentially there is a role in the third line or afterwards. We know that patients are going to be getting chemotherapy and amivantamab in the second-line setting. There is a need for further drugs and interventions in the third line if patients don't have other AGAs [actionable oncogenic alterations] or other drivers that we can use targeted therapies for. I am hesitant to give up completely on the drug. I do agree it's quite toxic and very disappointing to unfortunately see these results in the second line. Olazagasti: I agree. Moving on to the next study — Ana, do you want to talk to us about the SACHI study? Velazquez Mañana: The SACHI study was an open-label, randomized trial of savolitinib plus osimertinib vs platinum doublet chemotherapy in patients who, post EGFR TKI, had progressed in the second line and had a MET amplification. We know that MET amplifications are an extremely common mechanism of resistance to EGFR TKI-targeted therapies. Interestingly, in this study, which brings a little bit of heterogeneity, they included patients treated with first- and second-generation EGFR TKIsas well as those treated with third-generation TKIs like osimertinib, which would be our standard of care. They did look to make sure those were T790M negative, those treated with earlier generations. Interestingly, the results on the primary endpoint of progression-free survival (PFS) showed a benefit of 8.2 months in the combination vs 4.5 months in patients treated with doublet chemotherapy. That [benefit] was maintained in both patients treated with earlier-generation TKIs as well as those treated with third-generation TKIs. It also had some efficacy data and overall response rates of 63.2% vs 36.2%. Definitely, as we know, using a MET-targeted therapy is helpful. We already know from the United States that they use an approval in the second line of chemotherapy and amivantamab. That approach leads to responses in patients after EGFR TKIs. I think it's an interesting approach, obviously, to think of sparing patients from chemo in that second line and combining two TKIs, but we have to see if that is better than chemo with amivantamab would've been, which would've been our standard of care here. With savolitinib, we know what the adverse events are. It's a drug that's been approved in China now for years. It's not used in the United States, but I think, based on these studies, it's interesting to see what other studies will come in the future and whether this is a potential approach for us to use. Olazagasti: Definitely it's interesting. I feel like EGFR is the cool kid on the block now. We have so many options and so many studies looking into it, and it's just interesting to see what the future holds and what else is going to come into play. Continuing down the line of the EGFR second-line studies, I'm going to talk about the OptiTROP-Lung03 study. This study uses sacituzumab tirumotecan. It's a phase 3 study of EGFR mutants. Patients had to receive not only TKI but also platinum therapy, and they were randomized into using sacituzumab tirumotecan — we're going to call it sac-TMT because this is very hard to pronounce — vs docetaxel. The primary endpoints of the study were overall response rates, and secondary endpoints were PFS and OS. The study showed that the overall response rate was 45.1% vs 15.6% in the docetaxel arm. Also, there was a PFS benefit. The median PFS was 6.9 compared to only 2.8 in the chemo arm. Even though the median OS is still ongoing, with the median not reached yet, at 12 months there was an OS of 72.8% compared to 43.2%. I think this drug has been approved in China, and I know that in December it received breakthrough FDA designation in the United States. We'll see, again, what the future holds. Do you have any thoughts about this? Velazquez Mañana: We've been seeing from the different TROP2 ADCs that clearly they have a role in EGFR -driven lung cancer. I think it's exciting to see another one. Unfortunately, there are drugs that have many toxicities, so they are hard to manage for patients. Again, on this one I am a little bit conflicted with what the comparator arm is, and one that not necessarily would be our current standard of care. So we are having a large amount of new development and newer drugs, but because of how long it takes to run trials and the newer approvals that come, it's hard to make comparisons and decisions of which ones you should select and the timing of them. Hopefully, we'll get more data in the future. Olazagasti: I think that's the general consensus. And the dilemma that we have right now in the EGFR space, because we have so many approved options, is that there's really not a great sequential treatment. It's not really a one-size-fits-all approach. Some people use osimertinib alone in the first line. Some people use the FLAURA2 study with osimertinib and chemo. Some people prefer the MARIPOSA regimen. These are all pretty decent options, and so bringing these other drugs into the second- and third-line setting, how do we do the sequencing? I think that's really where the dilemma and the problems are going to come about. Institutions may have different orders and different preferences, but I think in these situations it's also important to take each patient into consideration individually because, like we have already mentioned, it's not only about the treatment and then the benefits, but also the side-effect profile. This one in particular didn't have any ILDs compared to in HERTHENA where they had a high rate, but we have to really look into toxicities because it's not only survival for patients and PFS; it's really about quality of life, too. With this great discussion, I think we're going to wrap up for today. Thank you to my friends and colleagues for joining me. Again, this is Coral Olazagasti, speaking from the 2025 ASCO Annual Meeting here in Chicago.
Yahoo
04-06-2025
- Business
- Yahoo
New Potential Treatment Strategy for Brain Metastases and Leptomeningeal Disease: HER3-DXd Shows Promising Results in the Phase II TUXEDO-3 Study for Patients With Limited Therapeutic Options
The TUXEDO-3 trial is the first study to evaluate the intracranial and extracranial efficacy and safety of a novel anti-cancer drug in patients with breast and lung cancer and active brain metastases, and leptomeningeal disease from solid tumors. These results were presented as an oral presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, with select results simultaneously published in Nature Medicine. MEDSIR's DEMETHER clinical trial was mentioned during abstract discussion due to the relevance of its strategy. CHICAGO, June 04, 2025--(BUSINESS WIRE)--Leading international medical research company, MEDSIR announced today the positive results of the TUXEDO-3 trial at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025. This phase II study funded by Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, evaluates the efficacy and safety of patritumab deruxtecan (HER3-DXd) in patients with active brain metastases and leptomeningeal disease, serious complications associated with advanced stages of the cancer. The study was carried out to evaluate HER3-DXd in patients with metastatic breast cancer (mBC) and advanced non-small cell lung cancer (aNSCLC) with active brain metastases, and patients with leptomeningeal disease from solid tumors. This is an antibody-drug conjugate to target HER3, a protein receptor found on the surface of cancer cells in brain metastases. HER3-DXd is an investigational agent consisting of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC Technology payload causes tumor DNA damage, killing cancer cells within and surrounding the tumor microenvironment The study showed promising results, which were presented today in an oral session. Results from the leptomeningeal cohort have been simultaneously published in the renowned journal Nature Medicine due to its potential benefit in patients with a high unmet medical need. In patients with breast cancer and brain metastases, intracranial responses were observed across all breast cancer subtypes, including luminal, HER2-positive, and triple-negative. A NEW HOPE FOR DIFFICULT-TO-TREAT METASTASES "This study represents a significant advancement in our understanding of how to treat brain metastases and leptomeningeal disease, and we are hopeful that our findings will pave the way for new, effective therapies for these patients," stated Dr. Matthias Preusser, MD, Medical Oncologist and Head of the Clinical Division of Oncology, Medical University of Vienna and Principal Investigator of TUXEDO-3. Dr. Rupert Bartsch, MD, PhD, Consultant Hematology and Medical Oncology, Medical University of Vienna, added: "Brain metastases and leptomeningeal disease represent severe complications in cancer, leading to increased morbidity and mortality, and HER3-DXd could be a promising therapeutic alternative for these patients." Read more about TUXEDO-3 here: SHOWCASING PROMISING COLLABORATIVE TRIALS AT ASCO MEDSIR's trial DEMETHER, an international, phase II trial exploring the maintenance of trastuzumab and pertuzumab following trastuzumab deruxtecan as induction treatment for HER2-positive recurrent metastatic breast cancer patients, was mentioned during today's Discussion of LBA1008. DEMETHER's strategy is to optimize the sequence to increase patients' progression free survival (PFS) while improving their quality of life. The relevance of this mention highlighted the ability of MEDSIR for anticipating patients' needs and designing strategical trials to keep on pushing the barriers of clinical research. MEDSIR active presence at the ASCO Annual Meeting 2025 reinforces its leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in cancer treatment, with the aim of not leaving any patient left behind. ABOUT MEDSIR For further information: View source version on Contacts Media Sergio Aguilar Eduardo Martín Espallargas
Business Wire
04-06-2025
- Business
- Business Wire
New Potential Treatment Strategy for Brain Metastases and Leptomeningeal Disease: HER3-DXd Shows Promising Results in the Phase II TUXEDO-3 Study for Patients With Limited Therapeutic Options
CHICAGO--(BUSINESS WIRE)--Leading international medical research company, MEDSIR announced today the positive results of the TUXEDO-3 trial at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025. This phase II study funded by Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, evaluates the efficacy and safety of patritumab deruxtecan (HER3-DXd) in patients with active brain metastases and leptomeningeal disease, serious complications associated with advanced stages of the cancer. "This study represents a significant advancement in our understanding of how to treat brain metastases and leptomeningeal disease" - Dr. Matthias Preusser. Share The study was carried out to evaluate HER3-DXd in patients with metastatic breast cancer (mBC) and advanced non-small cell lung cancer (aNSCLC) with active brain metastases, and patients with leptomeningeal disease from solid tumors. This is an antibody-drug conjugate to target HER3, a protein receptor found on the surface of cancer cells in brain metastases. HER3-DXd is an investigational agent consisting of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC Technology payload causes tumor DNA damage, killing cancer cells within and surrounding the tumor microenvironment The study showed promising results, which were presented today in an oral session. Results from the leptomeningeal cohort have been simultaneously published in the renowned journal Nature Medicine due to its potential benefit in patients with a high unmet medical need. In patients with breast cancer and brain metastases, intracranial responses were observed across all breast cancer subtypes, including luminal, HER2-positive, and triple-negative. A NEW HOPE FOR DIFFICULT-TO-TREAT METASTASES 'This study represents a significant advancement in our understanding of how to treat brain metastases and leptomeningeal disease, and we are hopeful that our findings will pave the way for new, effective therapies for these patients,' stated Dr. Matthias Preusser, MD, Medical Oncologist and Head of the Clinical Division of Oncology, Medical University of Vienna and Principal Investigator of TUXEDO-3. Dr. Rupert Bartsch, MD, PhD, Consultant Hematology and Medical Oncology, Medical University of Vienna, added: 'Brain metastases and leptomeningeal disease represent severe complications in cancer, leading to increased morbidity and mortality, and HER3-DXd could be a promising therapeutic alternative for these patients.' MEDSIR's trial DEMETHER, an international, phase II trial exploring the maintenance of trastuzumab and pertuzumab following trastuzumab deruxtecan as induction treatment for HER2-positive recurrent metastatic breast cancer patients, was mentioned during today's Discussion of LBA1008. DEMETHER's strategy is to optimize the sequence to increase patients' progression free survival (PFS) while improving their quality of life. The relevance of this mention highlighted the ability of MEDSIR for anticipating patients' needs and designing strategical trials to keep on pushing the barriers of clinical research. MEDSIR active presence at the ASCO Annual Meeting 2025 reinforces its leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in cancer treatment, with the aim of not leaving any patient left behind.
Yahoo
30-05-2025
- Business
- Yahoo
HER3-DXd shows promising results in the phase II TUXEDO-3 study for patients with limited therapeutic options
The TUXEDO-3 trial is the first study to evaluate the intracranial and extracranial efficacy and safety of a novel anti-cancer drug in patients with breast or lung cancer and active brain metastases, and leptomeningeal disease from solid tumors. These results were presented as an oral presentationat the American Society of Clinical Oncology (ASCO) 2025 annual meeting, with select results simultaneously published in Nature Medicine. The findings highlight HER3-DXd as a potential novel treatment for patients with secondary central nervous system involvement. CHICAGO, May 30, 2025 /PRNewswire/ -- Leading international medical research company, MEDSIR announced today the positive results of the TUXEDO-3 trial at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025. This phase II study funded by Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, evaluates the efficacy and safety of patritumab deruxtecan (HER3-DXd) in patients with active brain metastases and leptomeningeal disease, serious complications associated with advanced stages of the cancer. The study was carried out to evaluate HER3-DXd in patients with metastatic breast cancer (mBC) and advanced non-small cell lung cancer (aNSCLC) with active brain metastases, and patients with leptomeningeal disease from solid tumors. This is an antibody-drug conjugate to target HER3, a protein receptor found on the surface of cancer cells in brain metastases. HER3-DXd is an investigational agent consisting of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC Technology payload causes tumor DNA damage, killing cancer cells within and surrounding the tumor microenvironment The study showed promising results, which were presented today in an oral session. Results from the leptomeningeal cohort have been simultaneously published in the renowned journal Nature Medicine due to its potential benefit in patients with a high unmet medical need. In patients with breast cancer and brain metastases, intracranial responses were observed across all breast cancer subtypes, including luminal, HER2-positive, and triple-negative. Furthermore, some patients with breast cancer who had previously received antibody-drug conjugates also responded to HER3-DXd, highlighting the potential of HER3-DXd to overcome resistance and expand treatment options in refractory disease. Intracranial activity was also observed in patients with aNSCLC and brain metastases, intracranial responses were observed in patients whose tumors contained no activating driver mutations as well as patients whose tumors contained an EGFR or KRAS mutation. Overall, the data suggest that HER3-DXd may offer a novel treatment option for patients with secondary CNS involvement. KEY HIGHLIGHTS OF THE TUXEDO-3 STUDY The TUXEDO-3 study aimed to assess whether HER3-DXd could be an effective treatment option for patients with mBC and aNSCLC with active brain metastases, and leptomeningeal disease from solid tumors. The study met its primary objectives, with 23.8% and 30% patients achieving intracranial responses in active brain metastases from patients with mBC and aNSCLC, respectively, and 65% patients with leptomeningeal disease alive after 3 months. Side effects were consistent with previous studies using HER3-DXd. Tests evaluating quality of life and neurocognitive functions showed that patients remained stable or improved during the treatment follow-up. The primary objectives consisted of assessing the intracranial objective response rate in patients with active brain metastases from mBC and aNSCLC, and determining the number of patients with leptomeningeal disease alive after 3 months of starting the treatment. A NEW HOPE FOR DIFFICULT-TO-TREAT METASTASES "This study represents a significant advancement in our understanding of how to treat brain metastases and leptomeningeal disease, and we are hopeful that our findings will pave the way for new, effective therapies for these patients," stated Dr. Matthias Preusser, MD, Medical Oncologist and Head of the Clinical Division of Oncology, Medical University of Vienna and Principal Investigator of TUXEDO-3. Dr. Rupert Bartsch, MD, PhD, Consultant Hematology and Medical Oncology, Medical University of Vienna, added: "Brain metastases and leptomeningeal disease represent severe complications in cancer, leading to increased morbidity and mortality, and HER3-DXd could be a promising therapeutic alternative for these patients." ABOUT UMMET CANCER NEEDS Unmet cancer needs refer to gaps in resources, support, and treatment options that exist for cancer patients. Addressing unmet cancer needs is crucial to improving quality of life and outcomes for cancer patients. Through the collaborative work of healthcare providers, policymakers, and patient advocacy groups unmet cancer needs can be identified to help provide patients with comprehensive and quality care. SHOWCASING PROMISING COLLABORATIVE TRIALS AT ASCO In addition to the oral presentation of TUXEDO-3, MEDSIR will present both ADELA and WIN-B studies in poster format. The ADELA clinical trial is an ongoing international phase III study in collaboration with The Menarini Group, a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc., a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients. The study is being conducted across multiple countries which combines elacestrant with everolimus to treat advanced ER+/HER2- breast cancer with ESR1 mutations, aiming to delay disease progression. Regarding WIN-B, is a phase Ib/II, multi-center investigator-initiated trial, evaluating the safety and preliminary efficacy of combining Debiopharm's selective WEE1 inhibitor, Debio 0123 and Gilead's antibodydrug conjugate Trodelvy® (sacituzumab govitecan-hziy) in advanced HR+/HER2- and triple-negative breast cancers. MEDSIR active presence at the ASCO Annual Meeting 2025 reinforces its leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in cancer treatment, with the aim of not leaving any patient left behind. ABOUT MEDSIR Established in 2012, MEDSIR prides itself on working closely with its strategic partners to drive innovation in oncology research. Operating in Spain and the United States, the company provides end-to-end clinical trial management, from study design to publication, with an extensive global network of experts and integrated technology to streamline the process. The company offers proof-of-concept support and a strategic approach that enables research partners to benefit from the best of both worlds: industry clinical research and investigator-driven trials. With the aim of promoting independent research worldwide, MEDSIR has formed a strategic alliance with Oncoclínicas, the leading oncology group in Brazil, which offers outstanding research potential in South America. For further information: View original content to download multimedia: SOURCE MEDSIR Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
