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

A Study to Test How Zongertinib is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Hepatology

Zongertinib in HER2-altered gastrointestinal cancers: Preclinical activity and clinical findings from a phase Ia study (ESMO-GI 2025) - P1 | "In agreement with preclinical data, preliminary Ph Ia data indicate that zongertinib has encouraging clinical activity and manageable safety in pts with advanced, HER2-driven GI cancers."

P1 data • Preclinical • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

HER2 alterations in non-small cell lung cancer (NSCLC): from biology and testing to advances in treatment modalities. (PubMed, Front Oncol) - "Furthermore, we present updated clinical trial data for published HER2-targeted agents and explore ongoing clinical trials examining combinatorial therapies and next-generation HER2-targeted agents such as zongertinib, A166, ARX788, SHRA1811, and others. Given the rapid evolution in this field, our review offers a timely and comprehensive synthesis of the current state and future directions for HER2-altered NSCLC."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • TYK2

HER2 in Non-Small Cell Lung Cancer (NSCLC): Evolution of the Therapeutic Landscape and Emerging Drugs-A Long Way to the Top. (PubMed, Molecules) - "Despite numerous strengths, there is only one FDA/EMA-approved targeted therapy, an antibody-drug conjugate (ADC) called trastuzumab deruxtecan for pretreated patients with HER2 mutant NSCLC...But, two newly developed HER2-specific TKIs with low EGFR WT inhibition (BAY2927088 and zongertinib) reported encouraging results and received the breakthrough therapy designation from the FDA...A section of this paper is dedicated to the role of immunotherapy in HER2-altered NSCLC. The last section of this paper focuses on the drugs under development and their challenges."

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

Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments 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 | Trial completion date: Aug 2028 ➔ Sep 2029 | Trial primary completion date: Feb 2027 ➔ Sep 2029

Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Top 5 MD Anderson abstracts at AACR 2025 (MD Anderson Press Release) - "The American Association for Cancer Research (AACR) Annual Meeting showcases exciting new cancer therapies that help link translational science and clinical trials. MD Anderson researchers will be presenting more than 200 studies at AACR this year."

Clinical data • Non Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma

A Study to Test How Zongertinib is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology

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) - P1, P2 | "*Except breast cancer, gastric, gastroesophageal junction, or esophageal adenocarcinoma. †Except NSCLC."

Clinical • P2 data • Pan tumor • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Zongertinib in HER2-altered breast cancer: Preclinical activity and preliminary results from a phase Ia dose-escalation study. (ASCO 2025) - P1 | " Cell proliferation assays were undertaken in HER2-amplified BC cell lines (relative copy numbers ranging from 3.2–10.1) exposed to serial dilutions of zongertinib and tucatinib. Zongertinib potently inhibits HER2-driven BC growth in preclinical models in vitro and in vivo. Preliminary Ph Ia data indicate that zongertinib has encouraging clinical activity and manageable safety in pts with advanced, HER2-driven BC."

P1 data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • 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. (ASCO 2025) - P1 | "Zongertinib-treated patients reported a rapid improvement followed by stability in physical functioning and NSCLC-SAQ total score. The frequency and severity of patient-reported symptomatic AEs and the overall side effect burden demonstrated favorable tolerability of zongertinib."

Clinical • Metastases • Patient reported outcomes • Cough • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Pruritus • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • 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=416 | Recruiting | Sponsor: Boehringer Ingelheim | N=270 ➔ 416

Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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) - P1, P1/2 | "In Ph Ib, pts will receive escalating doses of zongertinib plus fixed-dose T-DM1, T-DXd, or capecitabine + trastuzumab (Table). Pts will remain on treatment until disease progression, undue toxicity or any other protocol-defined stopping criterion. Table: 409TiP"

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • 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 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: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Nov 2025 ➔ Nov 2026

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

Developing zongertinib for the treatment of HER2-mutant advanced NSCLC (PRNewswire) - "Patient reported outcomes (N=30) from the Beamion LUNG-1 study (NCT04886804) evaluating zongertinib, showed improvements in physical functioning and disease-related symptoms in previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC, identified through the following surveys: EORTC IL46/Q168 Survey (side effect burden): 80% to 90% (24 to 27) of patients reported 'not at all' or 'a little' side-effect trouble across all visits. PRO-CTCAE: Patient-reported symptomatic adverse events assessed were in line with the previously reported safety profile of zongertinib in the Beamion LUNG-1 study; the majority of patients who reported they experienced diarrhea stated 'rarely' or 'occasionally'."

Patient reported outcomes • Non Small Cell Lung Cancer

Promising results with zongertinib in advanced-stage HER2-mutant NSCLC. (PubMed, Nat Rev Clin Oncol) - No abstract available

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

Zongertinib in patients with pretreated HER2-mutant advanced NSCLC: Beamion LUNG-1 (AACR 2025) - P1 | "Zongertinib demonstrated significant and clinically meaningful activity with a manageable safety profile in pts with pretreated advanced NSCLC harboring HER2 mutations."

Clinical • Metastases • 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

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

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

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

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