Patient Reported Outcomes Show Improved Symptoms With Zongertinib for HER2-Mutated Non-Small Cell Lung Cancer

Zongertinib (Boehringer Ingelheim) yielded clinically meaningful improvements in disease-related symptoms, physical functioning, and symptomatic adverse events (AEs) in patients with human epidermal growth factor receptor 2 (HER2)-mutated non-small cell lung cancer (NSCLC). The patient-reported outcomes (PROs) from the Beamion LUNG-1 trial (NCT04886804) will be presented at the 2025 ASCO Annual Meeting in Chicago, Illinois.¹

TKIs binding to target proteins | Image Credit: © Justlight - stock.adobe.com

NSCLC is the most prevalent form of lung cancer, accounting for approximately 80% to 85% of cases. HER2 mutations occur in about 2% of all NSCLC diagnoses, which result in more aggressive, progressive disease. Zongertinib is a tyrosine kinase inhibitor designed to irreversibly block HER2 activity with high selectivity, minimizing toxicity by avoiding inhibition of EGFR. In the phase 1a/1b first-in-human study Beamion LUNG-1, zongertinib demonstrated favorable safety and efficacy.^2-4

PROs from the trial were collected using the EORTC QLQ-C30 physical functioning scale, the NSCLC-SAQ (assessing symptoms such as cough, dyspnea, pain, fatigue, and poor appetite), the EORTC IL46/Q168 (evaluating side effect burden), and 9 PRO-CTCAE items (including mouth/throat sores, taste changes, nausea, vomiting, diarrhea, rash, dry skin, itching, and numbness or tingling). These assessments were conducted on days 1, 8, and 15 of cycle 1, and on day 1 of cycles 2, 3, 5, 7, and 9. The PRO analysis included 30 patients with previously treated HER2-mutant NSCLC who received 120mg QD zongertinib.⁴

Changes from baseline to cycle 5 were analyzed for EORTC QLQ-C30 physical functioning scores (scale: 0–100, with higher scores indicating better functioning) and NSCLC-SAQ total scores (scale: 0–20, with lower scores indicating fewer symptoms) using a mixed model for repeated measures. EORTC IL46 (scored from 1 [‘Not at all’] to 4 [‘Very much’]) and PRO-CTCAE items (scored from 0 [‘Never’/‘None’] to 4 [‘Almost constant’/‘Very severe’]) were analyzed descriptively, and the maximum proportions of patients with baseline-adjusted scores were calculated.⁴

A post hoc analysis further contextualized findings using clinically meaningful thresholds and examined associations between patient-reported outcomes and clinical endpoints, including objective response.⁴

PRO completion rates remained high throughout the study, exceeding 86% across all time points. Longitudinal analysis using a mixed model for repeated measures (MMRM) demonstrated consistent improvements in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total scores, with rapid gains sustained through cycle 9. By cycle 5, the least squares mean change from baseline (CFB) was +9.6 (95% CI: 6.3 to 12.9) for physical functioning and -3.9 (95% CI: -4.8 to -2.9) for NSCLC-SAQ scores.⁴

Patients reported a generally low side effect burden, as measured by the EORTC IL46. The proportion of patients indicating a burden of ‘Quite a bit’ or ‘Very much’ remained consistent with baseline (6.7%) across most visits, with a modest increase to 10% observed only on cycle 1, day 15.⁴

The AEs were consistent with known toxicity profiles, with diarrhea being the most frequently reported symptom (baseline-adjusted maximum of 30% for ‘Frequent’ or ‘Almost constant’). Some patients reported severe intensity or significant interference for any adverse event.⁴

The PROs showed the promising potential of zongertinib as a therapeutic option for patients with HER2-mutated NSCLC.

REFERENCES

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). Updated May 14, 2025. Accessed May 29, 2025. https://clinicaltrials.gov/study/NCT04886804

2. A pharmacist’s guide to lung cancer and its key treatments. Pharmacy Times. April 23, 2025. Accessed May 29, 2025. https://www.pharmacytimes.com/view/a-pharmacist-s-guide-to-lung-cancer-and-its-key-treatments

3. HER2 and lung cancer. American Lung Association. January 22, 2025. Accessed May 29, 2025. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/her2

4. Sabari J, Nadal E, Hendriks L, et al. 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 Annual Meeting. May 30, 2025, to June 3, 2025. Chicago, IL. Abstract 8620