PRO results from the Beamion LUNG-1 trial in treatment-naïve patients with HER2-mutant advanced non-small cell lung cancer

Background:

Zongertinib is an irreversible tyrosine kinase inhibitor that selectively inhibits human epidermal growth factor receptor 2 (HER2) while sparing wild-type epidermal growth factor receptor (EGFR), thereby minimizing associated toxicities. Zongertinib recently received accelerated approval in the U.S. for patients with unresectable or metastatic nonsquamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain-activating mutations. Here, we report patient-reported outcomes (PROs) on NSCLC-related symptoms, physical functioning, symptomatic adverse events (AEs), and their burden in patients who received 120 mg zongertinib once daily (QD) as first-line treatment in Cohort 2 of the phase 1b Beamion LUNG-1 trial (NCT04886804).

Objectives:

Describe PROs from patients who received 120 mg zongertinib QD as first-line treatment in Cohort 2 of the Beamion LUNG-1 trial.

Methods:

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) physical functioning scale, Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLCSAQ) (domains: cough, dyspnea, pain, fatigue, and poor appetite), EORTC Item Library 46 (EORTC IL46) (overall side effect burden), and nine Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) symptoms (mouth and/or throat sores, taste changes, nausea, vomiting, diarrhea, rash, skin dryness, itching, and numbness/tingling) were collected on cycle 1, days 1, 8, and 15, and day 1 of cycles 2, 3, 5, 7, and 9, with each cycle lasting 21 days. Change from baseline (CFB) in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score was analyzed using a mixed model for repeated measures. Responders were defined as patients meeting within-patient meaningful improvements in PRO scores or maintaining low levels of baseline symptomatology/high functioning. EORTC IL46 (1 = “Not at all”; 4 = “Very much”) and PRO-CTCAE (for frequency/severity/interference items: 0 = “Never”/“None”/“Not at all” to 4 = “Almost constantly”/“Very severe”/“Very much”) were analyzed descriptively.

Results:

The PRO analysis set included 71 patients. High completion rates of over 85% were observed through cycle 7. Patients had low levels of symptomatology and high levels of physical functioning at baseline. Mean CFB analysis showed that patients reported rapid within-patient improvements in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score after the first week of treatment (from cycle 1, day 8), which were sustained over time. A high proportion of patients responded to treatment in terms of their PRO scores; at cycle 5, 70% of patients were responders for physical functioning, and 47% were responders for NSCLC-SAQ total score. There was a low side effect burden; at any postbaseline time point, a maximum of 8.4% of patients (n=6) reported being troubled by side effects of treatment “Quite a bit” or worse, supported by low proportions of patients reporting symptomatic AEs via PRO-CTCAE.

Conclusion:

Patients treated with first-line zongertinib reported a rapid improvement followed by stability in physical functioning and NSCLC-SAQ total score, with high proportions of patients qualifying as PRO responders. Zongertinib was well tolerated, as reflected by the low overall side effect burden and the low incidence and mild nature of patient-reported symptomatic AEs.

Funding: Boehringer Ingelheim.

Prior Presentations:

Presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, May 29–June 2, 2026, in Chicago, IL, USA.

© 2026 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting. All rights reserved.