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

Zongertinib in Asian patients with previously treated advanced HER2-mutant NSCLC (ESMO Asia 2025) - P1 | "Consistent with the overall global analysis, zongertinib elicited strong efficacy with a manageable safety profile in Asian patients with previously treated advanced HER2-mutant NSCLC."

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

Zongertinib in HER2-mutant advanced NSCLC: Impact of therapy line on efficacy (ESMO Asia 2025) - P1 | "This analysis indicates that zongertinib provides the most significant clinical benefit when used as a second-line treatment in a pre-treated patient population."

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

Absorption, Metabolism, Distribution and Excretion (ADME) and Absolute Bioavailability Assessment of Zongertinib in Healthy Male Volunteers. (PubMed, Clin Drug Investig) - P1 | "Zongertinib was rapidly absorbed with high absolute bioavailability. The unchanged zongertinib was the predominant form in plasma and excreta, with fecal excretion as the main elimination pathway. Metabolism occurred primarily through oxidation, with minor contributions from glucuronidation and glutathione conjugation."

Journal • Metabolic Disorders • HER-2

Zongertinib, a Novel HER2 Tyrosine Kinase Inhibitor, Maintains an Anticancer Activity for Trastuzumab Deruxtecan-Resistant Cancers Harboring HER2-Overexpression. (PubMed, Int J Mol Sci) - "Meanwhile, both DSR32 and DSR4 cells maintained HER2 activation; thus, zongertinib, a HER2-selective tyrosine kinase inhibitor, blocked the HER2 pathway, induced apoptosis, and inhibited colony formation. Overall, zongertinib can provide therapeutic relief to patients with HER2-overexpressing cancer who have developed resistance to T-DXd."

Journal • Gastric Cancer • Lung Cancer • Oncology • Solid Tumor • HER-2

FDA Awards Second Batch of National Priority Vouchers (FDA) - "Upon submission of a complete application, national priority voucher holders will receive a decision within months, a drastic reduction of the typical review timeline....The following products were selected following external applications and internal nominations from FDA review divisions: (i) Zongertinib for HER2 lung cancer...; (ii) Dostarlimab for rectal cancer..."

FDA event • Non Small Cell Lung Cancer • Rectal Cancer

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs in Japan; durvalumab, cemiplimab, zongertinib, and taletrectinib for lung cancer, pirtobrutinib and atezolizumab for lymphoma, durvalumab for bladder cancer, panitumumab plus sotorasib for colorectal cancer, and vorasidenib for glioma. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Bladder Cancer • Brain Cancer • Colorectal Cancer • Genito-urinary Cancer • Glioma • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Solid Tumor

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2034 ➔ Sep 2036

Monotherapy • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Beamion LUNG-3: A Study to Test Whether Zongertinib Helps People With Surgically Removed, Non-small Cell Lung Cancer With HER2 Mutations Compared With Standard Treatment (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Boehringer Ingelheim

Monotherapy • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preclinical intracranial activity of NVL-330, a selective HER2 tyrosine kinase inhibitor (AACR-NCI-EORTC 2025) - "In this preclinical study, NVL-330 was broadly and selectively active against HER2 oncogenic alterations and demonstrated favorable brain penetrance and/or intracranial activity compared to T-DXd, zongertinib, and sevabertinib. This differentiated preclinical profile supports the potential for NVL-330 to address a medical need for patients with HER2-driven cancers, including those with brain metastases."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • EGFR • HER-2

Beamion BCGC-1: A phase Ib/II, randomized, open-label, multicenter trial of oral zongertinib, alone or in combination, for the treatment of advanced HER2-positive metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC) (ESMO 2025) - P1/2 | "Beamion BCGC-1 (NCT06324357) is a Phase (Ph) Ib/II trial investigating zongertinib as monotherapy or plus T-DM1, T-DXd, or trastuzumab ± capecitabine in pts with HER2-positive mBC, and plus T-DXd in pts with HER2-positive mGEAC. Editorial acknowledgement Medical writing assistance was provided by Lucy Lettin, BSc, of Ashfield MedComms, an Inizio company, and funded by Boehringer Ingelheim. Legal entity responsible for the study Boehringer Ingelheim Funding Boehringer Ingelheim"

Clinical • Metastases • P1/2 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Preclinical and Clinical Activity of VRN101099, a Novel Covalent HER2 TKI for Metastatic HER2-Driven Solid Tumors (AACR-NCI-EORTC 2025) - "Although HER2-targeted therapies such as T-DXd and Zongertinib have demonstrated favorable outcomes in HER2-driven tumors, their efficacy remains limited, particularly in patients with brain metastasis and in those harboring specific activating mutations (e.g. S310F/Y). Pharmacokinetic analysis showed that VRN10 achieves sufficient target engagement at an 80mg Ctrough, and remains well tolerated up to 160mg, with no treatment-related adverse events (TRAEs). Together, preclinical and emerging clinical findings demonstrate VRN101099's promise as a therapeutic option for patients with HER2-positive or HER2-mutant solid tumors, including those with difficult-to-treat metastatic sites such as the brain and bone."

Late-breaking abstract • Metastases • Preclinical • Bladder Cancer • Brain Cancer • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • HER-2

Zongertinib in patients with pretreated HER2-mutant advanced NSCLC: Beamion LUNG-1 (JADPRO 2025) - "IntroductionHER2 Mutations in NSCLCHER2 mutations in NSCLC are an actionable oncogenic driver, mainly leading to constitutive activation of the ERBB2 signaling pathway and tumorigenesis.HER2 Exon 20 insertion mutations account for approximately 90% of all HER2-mutations in NSCLC.These mutations are generally found in patients with non-squamous NSCLC, particularly Asian patients (~20-30%).Historical Challenge in HER2+ NSCLCCurrent treatment options for HER2-mutated advanced NSCLC are limited and unsatisfactory.Chemotherapy can prolong the survival of patients but generally displays low response rates.The only FDA-approved therapy is trastuzumab deruxtecan (T-DXd), which has shown good anti-tumor activity (ORR: 58%) in the DESTINY-Lung01 trial.However, resistance to T-DXd eventually occurs, leading to disease progression and treatment failure.There is an unmet need for effective treatment options for patients whose disease progressed on prior anti-HER2..."

Clinical • Metastases • Dental Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • Stomatitis • EGFR • HER-2

Recent Advances in the Development and Clinical Use of HER2 Inhibitors in Non-Small Cell Lung Cancer. (PubMed, Biomolecules) - "The first anti-HER2 inhibitor, trastuzumab-deruxtecan, was approved for previously treated advanced NSCLC with HER2 mutations, which accounts for 2-4% of NSCLC. The first anti-HER2 antibody, trastuzumab, was approved for HER2-positive metastatic breast cancer in 1998, and a combination therapy comprising trastuzumab, pertuzumab, and docetaxel demonstrated efficacy in the first-line setting...However, HER2-specific TKIs, such as zongertinib and BAY2927088, have demonstrated encouraging results...Despite different targets of HER2 mutations in NSCLC and HER2 amplification/overexpression in breast cancer, the development of HER2-targeting agents has been more advanced in breast cancer than in NSCLC. Therefore, pivotal clinical studies in breast cancer may help in identifying more effective therapies for NSCLC."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Circulating tumor DNA (ctDNA) analysis following zongertinib treatment (tx) in patients (pts) with human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC): Phase Ia/Ib Beamion LUNG-1 study (ESMO 2025) - P1 | "As of Nov 2024, there were only weak correlative trends between HER2 VAF changes and responders or SD; correlative analysis with PD was limited by small pt numbers. Conclusions In this comprehensive ctDNA analysis of NSCLC pts, zongertinib led to impressive reductions in HER2 VAF within Cycle 1, highlighting the potential of ctDNA as a tool for monitoring early clinical efficacy."

Circulating tumor DNA • Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • TP53

Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1 (ESMO 2025) - P1 | "The most common TRAEs (all/grade 3) were diarrhea (54%/3%), ALT increased (18%/4%), AST increased (16%/3%), and dysgeusia and nausea (both 16%/0%). Conclusions First-line zongertinib elicited strong and clinically meaningful efficacy with a manageable safety profile in treatment-naïve pts with advanced HER2 -mutant NSCLC, underpinning its ongoing evaluation in the randomized phase III Beamion LUNG-2 study."

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

Synthesis of BI 1584142 and BI 1810631 (Zongertinib), Two Potent HER2 Inhibitors, Labeled With Carbon-14 and With Deuterium. (PubMed, J Labelled Comp Radiopharm) - "Therefore, a common carbon-14-labeled intermediate like the sulfoxide [14C]-8 was prepared in four radioactive steps and used to provide [14C]-1 and [14C]-2 in two and three extra steps, respectively. Deuterium-labeled 1 and 2 were also synthesized as internal standards, using piperazine-d8 and 4-aminopiperidine-d9 for bioanalytical studies and other studies."

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

Very first real-world data on zongertinib use in non-small cell lung cancer patients with HER2 mutations: A brief report (OGP-OGTC 2025) - "Zongertinib may be an effective and well-tol erated treatment option for HER2-mutant NSCLC patients even if they are heavily pretreated, have a reduced performance sta tus or have a history of pneumonitis and brain metastase."

Clinical • Real-world • Real-world evidence • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • HER-2

Clinical Pharmacology of Zongertinib, a Novel HER2-Specific Tyrosine Kinase Inhibitor (JADPRO 2025) - "Co-administration with ketoconazole (strong CYP3A4 inhibitor) increased zongertinib AUC0-inf by 2.7-fold and Cmax by **1.8-fold}$. Co-administration with rifampicin (strong CYP3A4 inducer) decreased zongertinib AUC0-inf by 81% and Cmax by 64%...Dose adjustments required with strong CYP3A4 inducers, which reduce the exposure of zongertinib to a clinically relevant extent (AUC reduction of 81%; CYP3A4 inducers may have lower clearance if it also modulates or decreases P-gp transporter). Exposure-response analysis confirmed the benefits of 120 mg QD dose (low AUC associated with fewer non-CT events than 160 mg in the US)."

Clinical • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2

Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC) - results from the Beamion LUNG-1 trial (JADPRO 2025) - P1 | "overall side effect impact and symptomatic adverse events EORTC IL46/Q168 extent troubled with side effects of treatment The vast majority of patients, 80% to 90% (24 to 27 patients), reported 'Not at All' or 'A Little' side effect trouble across all visits, with a moderate increase in those responding 'A Little' post-baseline. Very few patients reported either 'Quite a Bit' or 'Very Much' (Figure 2) EORTC QLQ-C30 physical functioning MMRM analysis shows a rapid Improvement which remains stable thereafter, LS mean change from baseline (95% confidence interval) at cycle 5: 9.6 (6.3, 12.9) and cycle 9: 7.8 (3.2, 12.5) (Figure 7) A consistent proportion of patients improved/were stable/deteriorated over time compared to baseline. Improvement peaks at cycle 5, with 53.3% of patients experiencing a meaningful improvement."

Clinical • Metastases • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pruritus • Pulmonary Disease • Solid Tumor • EGFR • HER-2

Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers. (PubMed, Future Oncol) - P1/2 | "Phase Ib (dose escalation) will determine the maximum tolerated dose of zongertinib plus trastuzumab emtansine (T-DM1), T-DXd, or trastuzumab ± capecitabine, in patients with HER2-positive mBC, and plus T-DXd in patients with HER2-positive mGEAC. The trial is actively recruiting in six countries globally. www.clinicaltrials.gov identifier is NCT06324357."

Journal • P1/2 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Data from the Phase Ib Beamion LUNG-1 trial evaluating zongertinib in treatment-naïve patients with advanced HER2 (ERBB2)-mutant NSCLC were presented for the first time at ESMO 2025 (GlobeNewswire) - "Confirmed response by blinded independent central review was 77%, with 96% of patients achieving disease control....Of the responders (77%), 8% of patients achieved complete response, 69% achieved partial response and 96% of patients achieved disease control. At data cut-off, median values for duration of response (DoR) and progression-free survival (PFS) were not yet mature, with 47% of patients remaining on treatment and encouraging 6-month rates for DoR of 80% and PFS of 79%."

P1 data • Non Small Cell Lung Cancer

Effects of zongertinib on physical functioning and symptoms for patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): Results from the Beamion LUNG-1 trial. (ASCOQLTY 2025) - P1 | "Zongertinib-treated patients reported rapid improvement followed by stability in physical functioning and NSCLC-SAQ total score. Frequency and severity of patient-reported symptomatic AEs and overall side effect burden demonstrated favorable tolerability of zongertinib."

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

Relative Bioavailability of Zongertinib, an Orally Administered HER2-Selective Tyrosine Kinase Inhibitor, under Fed and Fasted Conditions in Healthy Male Participants: Results from Two Randomized, Open-Label, Crossover Studies. (PubMed, Mol Pharm) - P1 | "Zongertinib demonstrated good bioavailability in healthy participants. A small dose-dependent food effect was observed."

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

Nonclinical and Clinical Assessments of an Optimized Tablet Formulation of the Novel HER2-Selective Tyrosine Kinase Inhibitor Zongertinib: Focus on Relative Bioavailability and Impact of Variation of Gastric pH. (PubMed, Mol Pharm) - "Geometric mean Cmax and AUC0-tz were similar after treatment with zongertinib SDD with and without rabeprazole. Zongertinib SDD formulation showed good bioavailability irrespective of pH, supporting further clinical development."

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

Zongertinib (Hernexeos) for NSCLC. (PubMed, Med Lett Drugs Ther) - No abstract available

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