34P Updated data from Beamion LUNG-1, a phase (ph) Ia/b trial of the HER2-specific tyrosine kinase inhibitor (TKI), zongertinib (BI 1810631), in patients (pts) with HER2 mutation-positive (m+) NSCLC

Beamion LUNG-1 is an ongoing first-in-human Ph Ia/b trial assessing zongertinib in pts with HER2 aberration-positive solid tumours (Ph Ia) and HER2 m+ NSCLC (Ph Ib; NCT04886804). Here, we present updated Ph Ia (29 Sept 2023 cut-off) and interim Ph Ib (31 July 2023 cut-off) data. Ph Ia recruited pts with HER2 aberration-positive (gene mutations or rearrangements, amplification or overexpression) advanced solid tumours who were treated with escalating doses of zongertinib BID (≥15 mg) or QD (≥60 mg). Primary endpoint: maximum tolerated dose (MTD). Ph Ib is recruiting patients with HER2 m+ advanced/metastatic NSCLC (Cohorts: 1, pre-treated HER2 TKD m+; 2, treatment Tx-naïve HER2 TKD m+; 3, previously treated non-TKD HER2 m+; 4, active brain metastases; 5, prior Tx with anti-HER2 antibody–drug conjugates). The primary endpoint was overall response rate (ORR) by investigator assessment. Ph 1a: pts (n=61) received zongertinib at 15/30/60/100/150 mg BID (n=3/3/4/4/3) and 60/120/180/240/300/360 mg QD (n=5/4/9/12/10/4). Median duration (range) of Tx: 4.8 (< 1─18.7) mos; ongoing in 35 pts. There were two dose-limiting toxicities during the MTD evaluation period (grade G 3 decreased platelets 360 mg QD; G3 diarrhoea 240 mg QD); the MTD was not reached for BID or QD. TRAEs (all/G3/G4/G5): 72/10/0/0%. Serious TRAEs: 2% (n=1; G3 AST/ALT). In 53 evaluable pts, ORR/disease control rate (DCR): 49/91%. Median DoR: 12.7 mos (95% CI: 4.2─12.7). In 36 evaluable NSCLC pts, ORR/DCR: 58/97%. As of 31 July 2023, 42 patients had been treated in Cohort 1 of Ph Ib (randomised to 120/240 mg QD). TRAEs (all/G3/G4/G5): 67/5/5/0%, most commonly diarrhoea (G1/G2/G≥3; 24/5/0%) and rash (17/5/0%). Most pts with diarrhoea (64%) had only one occurrence. Serious TRAEs: 5% (n=2; G4 decreased neutrophils, G4 immune thrombocytopenia). No AEs led to Tx discontinuation. ORR/DCR (n=23): 74/91%. All responding patients remained on Tx at data cut-off. Zongertinib was well tolerated and exhibited promising efficacy in pts with HER2 TKD m+ NSCLC. Prespecified futility analysis was passed. The trial is ongoing.