Hernexeos (zongertinib) / Boehringer Ingelheim, Sino Biopharm - LARVOL DELTA

Acquired Resistance to Zongertinib Treatment in Patients With HER2-Mutant NSCLC: Phase Ib Beamion LUNG-1 Study (IASLC-WCLC 2026) - P1 | "Acquired escape mechanisms were diverse, but resulted in an overall escape pattern, characterized by enhanced proliferation, metabolic reprogramming and potential reductions in tumor immunogenicity. Overall, these findings highlight the necessity of molecularly guided, patient-specific therapeutic strategies at disease progression."

Clinical • P1 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • CDKN2A • EGFR • ERBB4 • HER-2 • IFNA1 • IFNG • MYC • TP53

A Pooled Analysis of Zongertinib Treatment in HER2-Overexpressed/Amplified NSCLC (ESMO 2026) - No abstract available

Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Zongertinib in NRG1 fusion-positive solid tumors (ESMO 2026) - No abstract available

Oncology • Solid Tumor • NRG1

Beamion BCGC-1: Four new phase Ib/II cohorts to evaluate oral zongertinib with other agents in HER2-positive metastatic breast cancer (mBC) and metastatic colorectal cancer (mCRC). (ASCO 2026) - P1/2 | "Trial details for Cohorts A–K, evaluating zongertinib as monotherapy or combined with T-DM1, T-DXd, or trastuzumab ± capecitabine in patients (pts) with HER2-positive mBC, and with T-DXd in pts with HER2-positive metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC), have recently been published (Hurvitz et al, Future Oncol 2025)...Here, we report 4 new cohorts (L–O) to evaluate the efficacy and safety of zongertinib plus zanidatamab in HER2-positive mBC, or plus trastuzumab or mFOLFOX6 ± trastuzumab in HER2-positive mCRC...In Ph II, the primary endpoint is OR by RECIST v1.1; secondary endpoints include PFS, disease control, AEs leading to dose reduction, PK, and pt-reported outcomes. Pts will remain on treatment until any protocol-defined stopping criterion occurs."

Metastases • New P1/2 trial • P1/2 data • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Beamion BCGC-1: Phase Ib/II Trial of Zongertinib Monotherapy/Combination Therapy - Evaluation of a Cohort of Advanced HER2-Positive Metastatic Breast Cancer (JBCS 2026) - P1/2 | "The Beamion BCGC-1 trial (NCT06324357) is a phase Ib/II trial evaluating zongertinib monotherapy or combination therapy with T-DM1, T-DXd, trastuzumab ± capecitabine, or zanidatamab in patients with HER2-positive metastatic breast cancer (mBC) and gastric cancer (GC)/colorectal cancer (CRC), with eight participating centers from Japan. The primary endpoint of Phase II is ORR (RECIST v1.1), with secondary endpoints including progression-free survival (PFS), disease control, adverse events leading to dose reduction, pharmacokinetics (PK), and patient-reported outcomes. Treatment will continue until protocol-defined discontinuation criteria are met."

Combination therapy • Metastases • Monotherapy • P1/2 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Innovative Therapies for HER2-altered Non-Small Cell Lung Cancer: a Narrative Review. (PubMed, Crit Rev Oncol Hematol) - "Combination strategies with immune checkpoint inhibitors, such as platinum-based chemotherapy plus PD-L1 inhibitors, are also being actively investigated, although overlapping toxicities, particularly pulmonary adverse events, remain a key concern. This narrative review summarizes the clinicopathological features of HER2-altered NSCLC, critically evaluates emerging HER2-targeted therapies, and discusses future treatment directions."

IO biomarker • Journal • Review • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Beamion LUNG-2: A Study to Test Whether Zongertinib (BI 1810631) Helps People With Advanced Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment (clinicaltrials.gov) - P3 | N=428 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Beamion BCGC-1: A phase Ib/II trial of the HER2-selective tyrosine kinase inhibitor (TKI) zongertinib (BI 1810631) + trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) for patients with metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC). (ASCO-GI 2025) - P1, P1/2 | "Patients will remain on treatment until disease progression, undue toxicity or any other protocol-defined stopping criterion. Enrollment is ongoing."

Clinical • Metastases • P1/2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Rechallenge With Zongertinib After Trastuzumab Deruxtecan in HER2-Mutant Lung Cancer (IASLC-WCLC 2026) - "First-line combination therapy with cisplatin, pemetrexed, and pembrolizumab was initiated; however, the primary tumor progressed within 4 months. Subsequent treatments included docetaxel + ramucirumab, S1, and atezolizumab with progression-free survival (PFS) of 8, 1, and 1 months, respectively...After 7 months of Carboplatin + nab-paclitaxel treatment, owing to primary tumor enlargement, zongertinib was restarted as the eighth-line treatment...Conclusions : This report clearly demonstrates the complementary effects of the distinct mechanisms of action of zongertinib and T-DXd. Of particular interest, resistance to TKI therapy appeared reversible after intervening ADC treatment."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • FGFR3 • HER-2 • ROS1

More Than a Mutation: Prevalence of HER2 Overexpression, Amplification, and Mutations by Histology in NSCLC (IASLC-WCLC 2026) - "HER2-directed therapies, most notably trastuzumab deruxtecan, have shown clinical activity and have received regulatory approval for HER2-mutant lung adenocarcinoma, while the role of HER2 overexpression as a therapeutic biomarker remains less defined. Additional HER2-directed tyrosine kinase inhibitors, including zongertinib and sevebertinib, have also recently received accelerated approval, further expanding targeted treatment options...Concordance between HER2 IHC and FISH was limited, reinforcing that protein overexpression, amplification, and mutation often occur as distinct events in NSCLC. These findings emphasize the importance of systematic HER2 testing in NSCLC to identify patients who may benefit from HER2-targeted therapies."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • HER-2

Intracranial Outcomes and Treatment Response in HER2 (ERBB2)-Mutated Non-Small Cell Lung Cancer With Brain Metastases (IASLC-WCLC 2026) - "The median time to intracranial progression for patients who had active progressive brain metastases prior to the start of a given therapy was 7.4 months for pemetrexed-based regimens, 3.2 months for trastuzumab deruxtecan (T-DXd), and 1.6 months for other HER2 targeted therapies (eg, trastuzumab, TDM-1, afatinib)...Conclusions : Pemetrexed-based therapies and T-DXd each achieved only modest CNS disease control in this cohort, and intracranial progression as well as development of LMD were common in patients with existing brain metastases, despite most patients receiving radiation as well. Therapies with better CNS activity for HER2-mutated NSCLC are therefore needed, potentially with newly-approved tyrosine kinase inhibitors such as zongertinib and sevabertinib."

CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

On-Target Acquired Resistance to Zongertinib and Strategy to Overcome It - in Vitro Study usingHER2ex20 Insertion Models (IASLC-WCLC 2026) - "Methods : We examined efficacy of zongertinib, sevabertinib and other TKIs with HER2 inhibitory activity (erlotinib, afatinib, poziotinib, mobocertinib, and osimertinib) using murine pro-B-cell line (Ba/F3) models harboring one of three most common HER2 exon 20 insertions (A775_G776insYVMA (YVMA), G776delinsVC (VC) and P780_Y781insGSP (GSP)). Conclusions : These findings indicate that distinct compound mutations confer differential resistance to HER2-TKIs depending on the original HER2 exon 20 insertion. Zongertinib-resistant mutations, such as YVMA+S783A and GSP+G776C, remained sensitive to poziotinib, whereas compound mutations associated with poziotinib resistance, including YVMA+C805S and VC+C805S, were effectively inhibited by sevabertinib."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Zongertinib combined with T-DXd in HER2-positive metastatic gastric, gastroesophageal junction, or esophageal carcinoma (mGEAC): First results from a phase Ib/II dose-escalation trial. (ASCO 2026) - P1/2 | "No new safety signals were observed for zongertinib in combination with T-DXd; further dose escalation is ongoing. Encouraging clinical activity was observed in pretreated pts with HER2-positive mGEAC who had disease progression following prior trastuzumab-based therapy."

Metastases • P1/2 data • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • EGFR • HER-2

Acquired Resistance to Zongertinib in Patients With HER2Mutant Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "Introduction : Zongertinib, an irreversible HER2-selective tyrosine kinase inhibitor (TKI), has shown transformative efficacy in HER2-mutant non-small-cell lung cancer (NSCLC). The HER2 C805S mutation defines a distinct structural mechanism of therapeutic escape, for which sevabertinib and T-DXd represent rational salvage strategies. $$graphic_4E1AFEA6-6E73-4793-B424-27A121AFA9AB$$ $$graphic_3DE555C8-7179-4680-BFCA-A269ABEB97CD$$"

Clinical • Metastases • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • MTAP • PIK3CA

Clinical Characteristics, Genomic Subtypes, and Outcomes of HER2-Altered NSCLC: A Multicenter Real-World Study in Taiwan (IASLC-WCLC 2026) - "The use of antibody-drug conjugates (ADCs) was associated with improved OS (aHR 0.50; p<0.001), whereas TKIs for HER2 alterations (including afatinib, zongertinib, and BAY 2927088) were not. TP53 co-mutation identifies a clinically relevant high-risk subgroup, while the use of ADCs is associated with improved survival outcomes. These findings support integrated clinicogenomic risk stratification in clinical practice and provide a framework for designing prospective biomarker-driven trials to further optimize treatment sequencing and personalize therapeutic decision-making in HER2-altered NSCLC."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Respiratory Diseases • Solid Tumor • HER-2 • TP53

Zongertinib + Platinum-Pemetrexed Chemotherapy ± Pembrolizumab in Treatment-Naïve HER2-Mutant NSCLC: Phase IIa Platform Study (IASLC-WCLC 2026) - P2 | "Approximately 60 patients will be randomized 1:1, stratified by the presence of brain metastases, to either Arm A (oral zongertinib 120 mg once daily plus intravenous carboplatin AUC 5 or cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 , in 3-week cycles) or Arm B (the same regimen plus intravenous pembrolizumab 200 mg). The study will be conducted at approximately 19 sites in 8 countries. Results will inform the further development of zongertinib-based combination regimens in patients with treatment-naïve advanced/metastatic NSCLC with activating HER2 mutations."

IO biomarker • P2a data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2

Beamion LUNG-1 and LUNG-2: The zongertinib clinical program in patients with advanced HER2-mutant non-small cell lung cancer (AACR 2025) - P1, P3 | "Beamion LUNG-2 will evaluate treatment-naïve patients with advanced or metastatic non-squamous NSCLC harboring TKD HER2 mutations, comparing the efficacy/safety of zongertinib with the standard of care (pembrolizumab plus platinum-based chemotherapy [cisplatin/carboplatin and pemetrexed]). The primary endpoint is progression-free survival (RECIST v1.1 assessed by blinded independent centralized review). Key secondary endpoints include overall survival, ORR, duration of response, and patient-reported outcomes."

Clinical • IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Acquired Resistance to Zongertinib in Patients With HER2Mutant Advanced Non-Small Cell Lung Cancer (IASLC-WCLC 2026) - "Conclusions : Acquired resistance to zongertinib involves diverse genomic and histologic adaptations. The HER2 C805S mutation defines a distinct structural mechanism of therapeutic escape, for which sevabertinib and T-DXd represent rational salvage strategies."

Clinical • Metastases • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • MTAP • PIK3CA

Efficacy and Safety of TKI Versus ADC in Advanced or Metastatic HER2 Mutant Non-Small Cell Lung Cancer: A Metanalysis (IASLC-WCLC 2026) - "Notably, newer selective TKIs such as Zongertinib (ORR 71%) and Sevabertinib (ORR 64%) demonstrated superior efficacy compared to older pan-HER TKIs, such as Poziotinib (ORR 28-39%) and Pyrotinib (ORR 30%). However, ADCs were associated with a higher incidence of ILD/pneumonitis, whereas TKIs were more likely to cause diarrhea. These findings support the potential of newer HER2-specific TKIs as promising therapeutic options for HER2-mutant NSCLC, with an improved safety profile and efficacy."

ADC • Clinical • Metastases • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Independent CE Dinner Satellite Symposium: Empowering Oncology Teams in HER2 Testing: Applying the New NCCN Standards to Transform NSCLC Care (JADPRO 2026) - "4) Evaluate treatment pathways for HER2-altered NSCLC, including agents such as T-DXd, sevabertinib, and zongertinib and their indications. 6) Enhance communication across multidisciplinary teams to ensure complete testing orders, accurate interpretation, and timely patient navigation. 7) Describe the toxicity profiles of newer HER2-targeted therapies, including T-DXd and other emerging HER2-directed agents, and apply evidence-based strategies for early recognition, monitoring, supportive care, and management of treatment-related adverse events to improve patient safety and clinical outcomes"

Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2

Beamion Lung 1, a Phase Ia/Ib Trial of the HER2 TKI, BI 1810631 in Patients with Advanced Solid Tumors with HER2 Aberrations (IASLC-WCLC 2023) - P1 | "These preliminary data indicate that BI 1810631 is well tolerated and shows strong efficacy signals across all dose levels in patients with pre-treated HER2 aberration-positive solid tumors. Recruitment into Phase Ib is ongoing with the QD regimen. Updated Phase Ia data, and emerging Phase Ib data, will be presented."

Clinical • Metastases • P1 data • Anemia • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

A Study in Healthy Men to Test How Bosentan Influences the Amount of Zongertinib in the Blood (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

Zongertinib in patients with HER2-mutant NSCLC: Updated analysis of beamion LUNG-1 (ESMO Asia 2024) - P1 | "Conclusions Treatment with zongertinib led to high response rates, including preliminary activity in the CNS, and encouraging duration of response and PFS in pts with HER2 TKD-mutant NSCLC. Zongertinib demonstrated a manageable safety profile, with most TRAEs being low-grade, including both diarrhea and rash."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study. (PubMed, J Clin Oncol) - P1 | "Zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with HER2-altered tumors, including those with HER2-mutant NSCLC."

Journal • P1 data • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Exploring Patient Experiences With Zongertinib: Qualitative Interviews of US Patients in the Beamion LUNG-1 Trial (IASLC-WCLC 2026) - P1 | "Some participants reported known symptomatic side effects, which were generally described as fewer and less impactful on their daily life when compared to those experienced while on prior systemic treatments. Cough, the most frequently reported NSCLC-related symptom before treatment, was consistently described as meaningfully improved during zongertinib monotherapy."

Clinical • Interview • Cough • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • EGFR