Cardiotoxicity

April 28, 2025 New data from the Phase Ib Beamion LUNG-1 trial were presented at AACR and simultaneously published in The New England Journal of Medicine Data presented included an objective response rate (ORR) of 71%, with 7% of patients achieving complete responses (CR), and a 96% disease control rate (DCR) Previously unreported results, including median duration of response (DoR) of 14.1 months and median progression-free survival (PFS) of 12.4 months, indicate the potential for zongertinib to impact clinical practice Zongertinib continued to demonstrate a manageable safety profile, with low incidence of grade ≥3 drug-related AEs Boehringer Ingelheim reported new and updated data from the Beamion LUNG-1 trial evaluating zongertinib in previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC). The data were featured in the official press program at the American Association for Cancer Research (AACR) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine. “These data presented at AACR 2025 suggest that zongertinib may offer a new approach to treating patients with non-small cell lung cancer with activating HER2 mutations,” said the trial’s coordinating investigator, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, zongertinib would be the first oral, targeted treatment option that addresses an unmet need for these patients.” Data from the most recent analysis showed durable response and clinically meaningful results with zongertinib in previously treated patients with advanced NSCLC who have HER2 mutations within the tyrosine kinase domain (TKD) (N=75). The ORR was 71% (95% CI: 60-80), with 7% complete response, 64% partial response, and 96% disease control in previously treated patients. Additionally, zongertinib had intracranial activity in previously treated patients (n=27, who were evaluable) with brain metastases, with 41% achieving response and 81% disease control. At AACR 2025, the median DoR of 14.1 and median PFS of 12.4 months were presented for the first time. Itziar Canamasas, Global Head of Oncology at Boehringer Ingelheim, said: “Zongertinib has the potential to reset the benchmark for patients with HER2-mutant advanced non-small cell lung cancer, a patient population that has historically faced a poor prognosis. At Boehringer, we take cancer care personally; these updated data reaffirm our approach of addressing areas with high unmet need and letting our research guide us to where we can have the biggest impact for patients.” Initial results in patients with advanced NSCLC with HER2 mutations in the TKD, who were previously treated with both platinum-based chemotherapy and subsequent HER2-directed antibody drug conjugates (ADC) (N=31), demonstrated an ORR of 48% (95% CI: 32-65) with 97% (95% CI: 15-52) of patients achieving disease control. An exploratory cohort (n=20) that included previously treated patients with advanced NSCLC with HER2 mutations outside of the TKD demonstrated an investigator-assessed ORR of 30% (95% CI: 15-52) and a DCR of 65% (95% CI: 43-82). This is the largest known dataset of patients with previously treated advanced NSCLC who have HER2 mutations outside the TKD. Both of these data sets were presented at AACR 2025 and are included in The New England Journal of Medicine publication. The data presented at AACR 2025 demonstrated a manageable safety profile for zongertinib with no drug-related deaths, cases of interstitial lung disease (ILD) or cardiotoxicity reported. The most commonly reported adverse event (AE) was grade 1 diarrhea, with low incidence of grade ≥3 drug-related events (17%) in patients with TKD mutations (N=75). *Confirmed response by BICR according to RECIST v1.1 **Confirmed response by investigator review according to RECIST v1.1 *** Median DoR and median PFS are based on Kaplan Meier estimates Lung cancer claims more lives than any other cancer type1 and the incidence is set to increase to over 3 million cases worldwide by 2040.2 NSCLC is the most common type of lung cancer.3 The condition is often diagnosed at a late stage,4 and fewer than 3 in 10 patients are alive five years after diagnosis.5 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).6 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.7 Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan’s Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib. A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574), a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations. Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care. We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim’s generational commitment to driving scientific innovation is reflected by the company’s robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer’s ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com. References 1 World Health Organization Cancer Factsheet. https://www.who.int/news-room/fact-sheets/detail/cancer (Accessed April 2025). 2 International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: https://gco.iarc.fr/tomorrow/en (Accessed August 2024). 3 Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. 4 Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 5 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). https://seer.cancer.gov/statfacts/html/lungb.html (Accessed: August 2024). 6 Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012). 7 Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997. The content above comes from the network. if any infringement, please contact us to modify.

New data from the Phase Ib Beamion LUNG-1 trial were presented at AACR and simultaneously published in The New England Journal of Medicine Data presented included an objective response rate (ORR) of 71%, with 7% of patients achieving complete responses (CR), and a 96% disease control rate (DCR) Previously unreported results, including median duration of response (DoR) of 14.1 months and median progression-free survival (PFS) of 12.4 months, indicate the potential for zongertinib to impact clinical practice Zongertinib continued to demonstrate a manageable safety profile, with low incidence of grade ≥3 drug-related AEs INGELHEIM, Germany and RIDGEFIELD, Conn., April 28, 2025 /PRNewswire/ -- Boehringer Ingelheim reported new and updated data from the Beamion LUNG-1 trial evaluating zongertinib in previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC). The data was featured in the official press program at the American Association for Cancer Research (AACR) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine. "These data presented at AACR 2025 suggest that zongertinib may offer a new approach to treating patients with non-small cell lung cancer with activating HER2 mutations," said the trial's coordinating investigator, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, zongertinib would be the first oral, targeted treatment option that addresses an unmet need for these patients." Data from the most recent analysis showed durable response and clinically meaningful results with zongertinib in previously treated patients with advanced NSCLC who have HER2 mutations within the tyrosine kinase domain (TKD) (N=75). The ORR was 71% (95% CI: 60-80), with 7% complete response, 64% partial response, and 96% disease control in previously treated patients. Additionally, zongertinib had intracranial activity in previously treated patients (n=27, who were evaluable) with brain metastases, with 41% achieving response and 81% disease control. At AACR 2025, the median DoR of 14.1 and median PFS of 12.4 months were presented for the first time. Itziar Canamasas, Global Head of Oncology at Boehringer Ingelheim, said: "Zongertinib has the potential to reset the benchmark for patients with HER2-mutant advanced non-small cell lung cancer, a patient population that has historically faced a poor prognosis. At Boehringer, we take cancer care personally; these updated data reaffirm our approach of addressing areas with high unmet need and letting our research guide us to where we can have the biggest impact for patients." Additional analyses of previously treated patients with HER2 mutations demonstrated zongertinib's clinically meaningful results Initial results in patients with advanced NSCLC with HER2 mutations in the TKD, who were previously treated with both platinum-based chemotherapy and subsequent HER2-directed antibody drug conjugates (ADC) (N=31), demonstrated an ORR of 48% (95% CI: 32-65) with 97% (95% CI: 15-52) of patients achieving disease control. An exploratory cohort (n=20) that included previously treated patients with advanced NSCLC with HER2 mutations outside of the TKD demonstrated an investigator-assessed ORR of 30% (95% CI: 15-52) and a DCR of 65% (95% CI: 43-82). This is the largest known dataset of patients with previously treated advanced NSCLC who have HER2 mutations outside the TKD. Both of these data sets were presented at AACR 2025 and are included in The New England Journal of Medicine publication. The data presented at AACR 2025 demonstrated a manageable safety profile for zongertinib with no drug-related deaths, cases of interstitial lung disease (ILD) or cardiotoxicity reported. The most commonly reported adverse event (AE) was grade 1 diarrhea, with low incidence of grade ≥3 drug-related events (17%) in patients with TKD mutations (N=75). AACR 2025 presentation: summary of key efficacy endpoints *Confirmed response by BICR according to RECIST v1.1 **Confirmed response by investigator review according to RECIST v1.1 *** Median DoR and median PFS are based on Kaplan Meier estimates About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type1 and the incidence is set to increase to over 3 million cases worldwide by 2040.2 NSCLC is the most common type of lung cancer.3 The condition is often diagnosed at a late stage,4 and fewer than 3 in 10 patients are alive five years after diagnosis.5 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).6 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.7 About zongertinib Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan's Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib. A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574)4, a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations. About the Beamion clinical trial program Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care. About Boehringer Ingelheim in Oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim's generational commitment to driving scientific innovation is reflected by the company's robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer's ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. 1World Health Organization Cancer Factsheet. (Accessed April 2025). 2International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: (Accessed August 2024). 3Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. 4Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 5National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). (Accessed: August 2024). 6Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012). 7Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997. 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Zongertinib is up for an FDA decision in this year\'s third quarter. \n Boehringer Ingelheim unveiled new data from its top oncology prospect zongertinib, further backing the drug’s prowess in previously treated patients with advanced non-small cell lung cancer (NSCLC) who have the relatively rare human epidermal growth factor receptor 2 (HER2)- mutations within the tyrosine kinase domain (TKD). At this year’s American Association for Cancer Research (AACR) Annual Meeting in Chicago, the German drugmaker added durability and progression free survival (PFS) results to the breadth of data linked to zongertinib from the company’s formerly announced phase 1b Beamion LUNG-1 trial.In the study, Boehringer divided patients across five cohorts, but cohort 1, made up of 75 previously treated patients, took the orally administrated tyrosine kinase inhibitor (TKI) zongertinib 120 mg once a day and was powered as the primary analysis cohort. Here, Boehringer saw a median duration of response of 14.1 months and helped patients live longer without their disease getting worse for a median of 12.4 months, indicating the potential for the med to “impact clinical practice,” Boehringer said in a press release.  The results, which were published in The New England Journal of Medicine, add to zogertinib’s known spread of clinical results. That includes an objective response rate of 71%, a complete response rate of 7% (64% partial response) and a disease control rate of 96%, showing “nearly all patients benefiting from zongertinib,” Boehringer’s global head of oncology, SVP Itziar Canamasas, Ph.D., summed up in an interview with Fierce.All told, the data go to show that zongertinib could represent a “breakthrough” for the patient population, which typically experiences “quite aggressive” disease, Canamasas said. Beyond efficacy, no drug-related deaths, instances of interstitial lung disease or cardiotoxicity were reported in Lung-1, making for a risk/benefit profile that Boehringer believes is “unparalleled.”Zongertinib is up for an FDA decision in the third quarter of this year. If approved, the drug would be the first oral, targeted treatment option in the disease space, reflecting a key chemo-free option. It’s a “true precision oncology agent that was beautifully designed,” Canamasas mused, meant to inhibit only HER2 and not target EGFR, another more common NSCLC mutation. HER2 mutations are typically associated with breast and gastric cancers but make up around 2% of lung cancer patients, typically in those who never smoked. “Until recently, there were no effective targeted therapies for HER2-mutated NSCLC,” coordinating trial investigator John V. Heymach, M.D., Ph.D., explained in the AACR release on the data. “This potentially practice-changing approval of zongertinib would provide access to a highly efficacious treatment option with a manageable safety profile and would be the first oral therapy and only tyrosine kinase inhibitor approved for patients with HER2-mutated NSCLC.”Lung cancer, in all its forms, is the second most commonly diagnosed cancer in the U.S., with about 250,000 diagnoses each year. For patients with metastatic NSCLC, prognosis is poor, with only around 8% living beyond five years after diagnosis.  AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu is currently the only drug cleared to treat NSCLC patients with tumors that have an activating HER2 mutation, leaving plenty of room for other treatment options. Enhertu carries risks of “significant” side effects and isn’t effective in all patients, Heymach explained in the AACR release on the data, as they look ahead for their drug\'s launch angle. Enhertu nabbed that accelerated FDA approval as the first HER2-directed med for patients with previously treated HER2-mutant metastatic NSCLC, back in 2022. The data for that green light came from the Destiny-Lung02 phase 2 test. This trial, made from an interim efficacy analysis in a prespecified patient cohort, showed a confirmed ORR of 57.7% (in 52 patients), with a complete responses seen in 1.9% of patients and partial responses in 55.8% of patients, all with a median duration of response of 8.7 months. Wrapped up with Boehringer\'s new durability data were encouraging results from an exploratory cohort of Lung-1, in which zongertinib achieved a disease control rate of 65% in previously treatment patients with HER2 mutations outside of the TKD. Meanwhile, in another cohort of those with HER2 mutations in the TKD who were previously treated with chemotherapy and HER2-directed ADCs, 97% of patients saw disease control and the overall response rate stood at 48%.Zongertinib is a “pipeline within a product” for Boehringer and could make a “huge impact to so many cancer patients,” Canamasas said. The drug is also being studied in a phase 3 trial that weighs it against the standard of care in first line HER2-mutated NSCLC, plus in an ongoing pan-tumor trial