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.

Abstract

8620 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 Ia/Ib first-in-human study evaluating safety and efficacy of zongertinib in patients with HER2-mutant advanced NSCLC (Phase Ib). Here, we report PRO data on NSCLC-related symptoms, physical functioning, symptomatic adverse events (AEs) and their burden from Phase Ib Cohort 1. The PRO analysis included patients with previously treated HER2-mutant NSCLC who received 120mg QD zongertinib. Methods: EORTC QLQ-C30 physical functioning scale, NSCLC-SAQ (cough, dyspnea, pain, fatigue and poor appetite), EORTC IL46/Q168 (side effect burden) and nine PRO-CTCAE items (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. 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 of 30 patients. High completion rates were observed, over 86%, across PROs and visits. Longitudinal MMRM analysis showed improvements for EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score, with rapid improvement which was maintained to cycle 9; CFB to cycle 5: LS means 9.6 (95% CI: 6.3, 12.9), and -3.9 (95% CI: -4.8, -2.9) respectively. Patients reported low overall side effect burden (EORTC IL46); patients reporting side effect burden on treatment as ‘Quite a bit’/ ‘Very much’ was equal to baseline reporting (6.7%), with the exception only 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. Clinical trial information: NCT04886804 .