(299) Patient-reported outcomes evaluating physical functioning and symptoms in patients with pretreated human epidermal growth factor receptor 2-mutant advanced non-small cell lung cancer - results from the Beamion LUNG-1 trial

Background: : Zongertinib is an irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing EGFR, thereby limiting associated toxicities. Beamion LUNG-1 (NCT04886804) is a Phase (Ph) la/lb first-in-human study evaluating safety and efficacy of zongertinib in patients with HER2-mutant advanced NSCLC (Ph lb).

Objective: : To report PRO data on NSCLC-related symptoms, physical functioning, symptomatic adverse events (AEs) and their burden from Ph lb Cohort 1.

Methods: : The PRO analysis included patients with previously treated HER2-mutant NSCLC who received 120 mg QD zongertinib. EORTC QLQ-C30 physical functioning scale, NSCLC-SAQ scores, EORTC IL46/Q168 (side effect burden) and 9 PRO-­CTCAE items were collected on days 1, 8 and 15 (cycle 1) and day 1 (cycles 2, 3, 5, 7, 9). Change from baseline (CFB) to cycle 5 in EORTC QLQ­-C30 physical functioning (0-100, higher=better) and NSCLC-SAQ total score (0-20, lower=fewer symptoms) were analyzed using mixed model repeated measures. EORTC IL46 (1='Not at all', 4='Very much') and PRO-CTCAE (0=Never/None to 4=Almost Constant/Very Severe) were analyzed descriptively; maximum baseline-adjusted proportions of patients were calculated. Post-hoc analysis includes contextualizing results based on clinically meaningful thresholds and exploring associations between PRO and clinical endpoints such as objective response.

Results: : The PRO analysis set comprised 30 patients. Completion rates were >86% across PROs and visits. Longitudinal MMRM analysis showed rapid improvements on EORTC QLQ-C30 physical functioning (CFB to cycle 5: LS means 9.6 [95% Cl: 6.3, 12.9]) and NSCLC-SAQ total score (-3.9 [95% Cl: -4.8, -2.9]) that was maintained to cycle 9. Patients reported low overall side effect burden (EORTC IL46); the percentage of patients reporting side effect burden as 'Quite a bit'/'Very much' was equal to baseline (6.7%), except at cycle 1 day 15 (10%). Patient reported adverse event frequency/severity (PRO-CTCAE items) reflected expected toxicity profiles; diarrhea was reported at the highest frequency (maximum baseline adjusted: 'Frequent'/'Almost constant'=30%), low percentages of patients reported high levels of severity or interference for any adverse event.

Conclusions: : 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.

Sponsorship:: Boehringer Ingelheim