102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

First-line (1L) SoC for pts with HER2-mutation positive (HER2m+) NSCLC is platinum-based chemotherapy ± immunotherapy. To date, no targeted 1L treatments (txs) have been approved. Zongertinib is a HER2-selective tyrosine kinase inhibitor that binds to wild-type and mutated HER2, sparing EGFR. In Phase Ia of Beamion LUNG-1 (NCT04886804), zongertinib conferred objective response (OR)/disease control rates of 49/91% in pts with pretreated HER2 aberration-positive solid tumours, and 58/97% in those pts with HER2m+ NSCLC, with manageable safety with few EGFR-associated adverse events. Here, we describe Beamion LUNG-2 (NCT06151574), a phase III, randomised, controlled, open-label trial which will compare the efficacy and safety of 1L zongertinib with SoC in pts with HER2m+, locally advanced/metastatic non-squamous NSCLC. ∼270 pts will be randomised 1:1 to receive either zongertinib or SoC. Key inclusion criteria: histologically/cytologically diagnosed advanced/metastatic non-squamous NSCLC; no prior systemic tx for locally advanced/metastatic disease; HER2 mutation in the TKD; ≥1 measurable lesion (RECIST 1.1). Key exclusion criteria: tumours that have alterations with available therapy, and radiotherapy/major surgery ≤4 weeks prior to randomisation. In the experimental arm, 120 mg oral zongertinib QD will be given in 21-day cycles. In the comparator arm, 500 mg/m2 intravenous pemetrexed chemotherapy plus either 75 mg/m2 cisplatin or Area Under the Curve 5 carboplatin, plus 200 mg pembrolizumab will be given on Day 1 q3w for four cycles, followed by 500 mg/m2 pemetrexed plus 200 mg pembrolizumab q3w for ≤35 cycles. In both arms, tx will continue until progressive disease (RECIST 1.1), undue toxicity, or other criteria are met. Primary endpoint: progression-free survival (RECIST 1.1). Secondary endpoints: OR (defined as best overall response of complete or partial response, RECIST 1.1); pt-reported outcomes (changes from baseline to Week 25); overall survival; and adverse events during the on-treatment period (CTCAE 5.0). NCT06151574. Medical writing support for the development of this abstract, under direction of the authors, was provided by Ellie Sherwood MPhil, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim. Boehringer Ingelheim. Boehringer Ingelheim.