Primary Phase Ib Analysis of Beamion LUNG-1: Zongertinib (BI 1810631) in Patients with HER2 Mutation-Positive NSCLC

Introduction: Zongertinib is a novel, orally administered HER2-specific TKI that binds selectively and covalently to the HER2-TKD, sparing WT EGFR and limiting EGFR-related AEs. In Nov 2023, zongertinib was granted Fast Track Designation (US FDA) as an invest. treatment (Tx) for pts with adv/met HER2 mutation-pos. (m+) NSCLC who had PD on/after platinum-based therapy. Beamion LUNG-1 is an ongoing, Ph Ia/Ib, first-in-human, open-label study, evaluating the safety and efficacy of zongertinib in pts with HER2 aberration-pos. (abr+) solid tumors (Ph Ia) and HER2m+NSCLC (Ph Ib). In Ph Ia (May 2024 cut-off), zongertinib conferred confirmed ORR/DCR of 32.3/87.9% in pts with pretreated HER2abr+solid tumors (all dose levels), and 35.8/94.3% in pts with HER2m+NSCLC, with few manageable EGFR-related AEs. MTD was NR; doses in dose optimization were 120/240 mg QD. Here, we report results from Ph Ib Cohort 1.

Methods: Ph Ib is recruiting pts with HER2m+adv/met NSCLC into 5 cohorts: 1. pre-treated HER2 TKDm+; 2. Tx-naïve HER2 TKDm+; 3. pre-treated non-TKD HER2m+; 4. active BMs; and 5. prior Tx with anti-HER2 ADC. Cohort 1: initial randomization to 120 (selected at interim analysis)/240 mg zongertinib QD; prim. endpoint: OR by BICR, sec. endpoints: DoR and PFS.

Results: As of May 2024, 132 pts have been treated in Ph Ib Cohort 1 with zongertinib at 120 mg/240 mg QD (n=75/57). 57.6% were female; median age at BL was 62 years (range: 30-82). Further results are summarized in [Fig. 1]:

Fig. 1  

Conclusions: Z was well tolerated and demonstrated promising efficacy in pts with HER2m+NSCLC; the prim endpoint of Beamion LUNG-1 Ph Ib Cohort 1 was met.

Publikationsverlauf

Artikel online veröffentlicht:
18. März 2025