PRO results from the Beamion LUNG-1 trial in treatment-naïve patients with HER2 -mutant advanced NSCLC.

8616 Background: Zongertinib is an irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities. Here, we report patient-reported outcomes (PROs) on NSCLC-related symptoms, physical functioning, symptomatic adverse events (AEs) and their burden, from patients who were given 120 mg zongertinib QD as first-line in Cohort 2 of the Phase Ib Beamion LUNG-1 trial (NCT04886804). Methods: EORTC QLQ-C30 physical functioning scale, NSCLC-SAQ (domains: cough, dyspnea, pain, fatigue and poor appetite), EORTC IL46 (overall side effect burden) and nine PRO-CTCAE symptoms (mouth and/or throat sores, taste changes, nausea, vomiting, diarrhea, rash, skin dryness, itching, and numbness/tingling) were collected at cycle 1: days 1, 8 and 15, and day 1 of cycles 2, 3, 5, 7 and 9, each cycle being 21 days. Change from baseline (CFB) in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score were analyzed using mixed model repeated measures. The proportion of patients regarded as responders was defined as patients meeting within-patient meaningful improvements in PRO score 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 were observed, over 85% up to cycle 7. Patients had low levels of symptomatology and high levels of physical functioning at baseline. Mean CFB analysis showed 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 score; at cycle 5, 70% of patients were responders for physical functioning, and 47% of patients for NSCLC-SAQ total score. There was low side-effect burden; at any post-baseline timepoint a maximum of 8.4% of patients n=6 reported being troubled with side-effects of treatment ‘Quite a bit’ or worse; supported by low proportions of patients reporting symptomatic adverse events via PRO-CTCAE. Conclusions: 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 adverse events. Clinical trial information: NCT04886804 .