zongertinib (BI 1810631) / Boehringer Ingelheim, Sino Biopharm - LARVOL DELTA

Zongertinib in Previously Treated HER2-Mutant Non-Small-Cell Lung Cancer. (PubMed, N Engl J Med) - P1 | "Zongertinib showed clinical benefit with mainly low-grade adverse events in patients with previously treated HER2-mutant NSCLC. (Funded by Boehringer Ingelheim; Beamion LUNG-1 ClinicalTrials.gov number, NCT04886804.)."

Journal • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

AACR: HER2 targeted therapy shows promise in previously treated lung cancers (MD Anderson Press Release) - P1 | N=554 | Beamion LUNG-1 (NCT04886804) | Sponsor: Boehringer Ingelheim | "The HER2-targeted therapy zongertinib demonstrated clinical benefits for previously treated patients with advanced HER2-mutant non-small cell lung cancer – particularly those with specific HER2 mutations – with manageable side effects, according to results from the Phase Ia/Ib Beamion LUNG-1 trial led by researchers from The University of Texas MD Anderson Cancer Center...The trial previously reported a 71% objective response rate (ORR) – indicating tumor shrinkage – in 75 patients from the first cohort, but newly presented data include a median duration of response (DOR) of 14.1 months and progression free survival (PFS) of 12.4 months....Grade three or higher adverse events occurred in 17% of patients and mostly included diarrhea and rash, with no instances of interstitial lung disease."

P1 data • Non Small Cell Lung Cancer • HER-2

VRN101099: A novel treatment option for HER2-driven cancer patients, overcoming T-DXd resistance and brain metastases (AACR 2025) - "In intracranial xenograft models, VRN101099 demonstrated superior anti-tumor efficacy to tucatinib, neratinib, zongertinib, trastuzumab, and T-DXd. In conclusion, VRN101099 is a promising HER2-selective TKI with a favorable profile including potency, tolerability, and brain permeability. This identifies VRN101099 as a potential novel systemic treatment option for patients with HER2-driven cancers, particularly those with brain metastases or those who have progressed after or failed with T-DXd."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Beamion BCGC-1: A Phase Ib/II dose escalation/optimization, randomized, open-label trial of oral zongertinib alone or in combination for advanced HER2-positive metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC) (ESMO-BC 2025) - No abstract available

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

Zongertinib demonstrates potent efficacy against cancer cells harboring HER2 non-tyrosine kinase domain mutations (AACR 2025) - "While tyrosine kinase inhibitors (TKIs) such as the HER2-selective inhibitor zongertinib and the pan-HER inhibitors poziotinib, pyrotinib, and afatinib have been tested primarily in patients harboring TKD mutations, their efficacy against non-TKD mutations has been less well characterized. Consistent with our results obtained using Ba/F3 models, HCC4006 HER2 V659E cells were sensitive to HER2 inhibition with zongertinib. Our findings indicate that zongertinib demonstrates comparable or more potent inhibitory activity for HER2 non-TKD mutants (e.g TMD and JMD) as HER2 TKD mutations, providing a potential therapeutic option for patients with these HER2 non-TKD mutant cancers."

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

The effect of food on zongertinib plasma exposure in healthy volunteers (AACR 2025) - P1 | "Taking zongertinib 240 mg after a high-fat, high-calorie meal resulted in an ~26% increase in plasma zongertinib exposure, which is not considered clinically relevant, and reduced overall between-subject variability in exposure compared with taking it under fasted conditions. Zongertinib was safe and well tolerated, with no unexpected safety findings reported. Zongertinib can be administered with or without food."

Clinical • Late-breaking abstract • Oncology • EGFR

Absorption, distribution, metabolism and excretion (ADME) properties and absolute bioavailability of zongertinib, a selective oral HER2-specific tyrosine kinase inhibitor, in healthy male subjects (AACR 2025) - "Zongertinib was rapidly absorbed with high absolute bioavailability. Unchanged zongertinib was the predominant component without any major metabolite circulating in plasma. Zongertinib was metabolized via oxidation, glucuronidation, and glutathione conjugation."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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

Enhanced HER2 internalization by clathrin-dependent endocytosis in non-small cell lung cancer positive for HER2 mutations (AACR 2025) - "Upregulation of HER2 phosphorylation promotes internalization of mutant forms of HER2 mediated by clathrin-dependent endocytosis, which may contribute to the efficacy of HER2-targeted ADCs in NSCLC positive for HER2 mutations."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

Zongertinib in patients with pretreated HER2-mutant advanced NSCLC: Beamion LUNG-1 (AACR 2025) - "Abstract is embargoed at this time."

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

Beamion PANTUMOR-1: A phase II, multicenter, multicohort, open-label trial to evaluate the efficacy and safety of the oral HER2-selective tyrosine kinase inhibitor zongertinib for the treatment of HER2-mutated or overexpressed/amplified solid tumors. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06581432 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P2 data • Pan tumor • Oncology • Solid Tumor • HER-2

Zongertinib in HER2-altered breast cancer: Preclinical activity and preliminary results from a phase Ia dose-escalation study. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT04886804 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

P1 data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • 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

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With HER2 Alterations: A Phase Ia Dose-Escalation Study (J Clin Oncol) - P1a | N=554 | Beamion LUNG-1 (NCT04886804) | Sponsor: Boehringer Ingelheim | "As of May 23, 2024, 105 patients were treated....The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response was 12.7 months (95% CI, 6.9 to NR). In 54 patients with NSCLC, confirmed ORR was 35% (95% CI, 24 to 49). Activity was observed in patients with A775_G776insYVMA (ORR, 38%) and those who had received previous HER2-directed therapy (ORR, 28%). In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR)."

P1 data • Non Small Cell Lung Cancer

BEAMION-Lung 1: Beamion LUNG-1: A Study to Test Different Doses of Zongertinib in People With Different Types of Advanced Cancer (Solid Tumours With Changes in the HER2 Gene) (clinicaltrials.gov) - P1 | N=554 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jan 2028 ➔ Aug 2028 | Trial primary completion date: Mar 2026 ➔ Dec 2026

Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NRG1

Boehringer’s zongertinib receives Priority Review from U.S. FDA for the treatment of HER2 (ERBB2)-mutant advanced non-small cell lung cancer (PRNewswire) - "Boehringer Ingelheim today announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review to its new drug application for zongertinib (BI 1810631) for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) mutations and who have received prior systemic therapy....The Prescription Drug User Fee Act (PDUFA) action date is in the third quarter of 2025....The application was based on results from the positive Phase Ib Beamion LUNG-1 trial."

Evidence highlight • FDA approval • Priority review • Non Small Cell Lung Cancer • HER-2

Zongertinib (BI 1810631) in Japanese patients with pretreated HER2 TKD-mutant NSCLC: Beamion LUNG-1 Phase Ib Cohort 7 (JSMO 2025) - No abstract available

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Zongertinib in patients with HER2-mutant NSCLC: updated analysis of Beamion LUNG-1 (JSMO 2025) - No abstract available

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

Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib in Combination With Trastuzumab Deruxtecan or With Trastuzumab Emtansine and to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread (clinicaltrials.gov) - P1/2 | N=582 | Recruiting | Sponsor: Boehringer Ingelheim | N=240 ➔ 582

Enrollment change • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • Oncology • Solid Tumor

A Study to Test How Zongertinib is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

Very first real-world data on zongertinib use in non-small cell lung cancer patients with HER2 mutations: A brief report. (PubMed, Cancer Treat Res Commun) - "Zongertinib may be an effective and well-tolerated treatment option for HER2-mutant NSCLC patients even if they are heavily pretreated, have a reduced performance status or have a history of pneumonitis and brain metastases."

Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • 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

…Zongertinib, a blockbuster innovative drug for lung cancer, has successfully submitted its marketing authorization application in China [Google translation] (Sino Biopharm Press Release) - "On January 15, Boehringer Ingelheim, a strategic partner of Sino Biopharmaceuticals, announced that the company has submitted a marketing authorization application for zongertinib, an innovative lung cancer drug under development, to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) and has been accepted. This new drug application is mainly based on the results of a Phase Ib clinical study, the BEAMION LUNG-1 trial, for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) who carry HER2 (ERBB2) activating mutations and have previously received systemic treatment."

China filing • Non Small Cell Lung Cancer

The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers. (PubMed, Pharmacotherapy) - "Zongertinib exposure was reduced by 63.5% when coadministered with the strong CYP3A inducer, carbamazepine."

Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

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=270 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2028 ➔ Jan 2027 | Trial primary completion date: Mar 2027 ➔ Nov 2025

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