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

G Ruiter; H Tu; M Ahn; K Yoh; J Zugazagoitia; E Smit; Y Wu; D Planchard; B Cho; B Wehler; Y Zhao; T Wehler; U von Wangenheim; M Rohrbacher; B Sadrolhefazi; G Lin; Y Yu; E Nadal; J Heymach

doi:10.1055/s-0045-1804642

Pneumologie, Table of Contents

Pneumologie 2025; 79(S 01): S48
DOI: 10.1055/s-0045-1804642

Abstracts

B1 – Pneumologische Onkologie

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

G Ruiter

¹Netherlands Cancer Institute

,

H Tu

²Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences)

,

M Ahn

³Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; Cois: Advisory Board Participation for Bms, Ariad and Lilly.

,

K Yoh

⁴National Cancer Center Hospital East

,

J Zugazagoitia

⁵12 de Octubre Hospital

,

E Smit

⁶Netherlands Cancer Institute, Leiden University Medical Center

,

Y Wu

⁷Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences; Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences)

,

D Planchard

⁸Institut Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers

,

B Cho

⁹Yonsei Cancer Center, Yonsei University College of Medicine,; Division of Medical Oncology,

,

B Wehler

¹⁰Universitätsklinikum Gießen Marburg GmbH Standort Gießen, Medizinische Klinik Iv/V

,

Y Zhao

¹¹The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital

,

T Wehler

¹²Universitätsklinikum Gießen und Marburg GmbH

,

U von Wangenheim

¹³Boehringer Ingelheim Pharma GmbH & Co. Kg

,

M Rohrbacher

¹⁴Boehringer Ingelheim International GmbH

,

B Sadrolhefazi

¹⁵Boehringer Ingelheim Pharmaceuticals, Inc.

,

G Lin

¹⁶Fujian Cancer Hospital

,

Y Yu

¹⁷Harbin Medical University Cancer Hospital

,

E Nadal

¹⁸Catalan Institute of Oncology, L'hospitalet

,

J Heymach

¹⁹MD Anderson Cancer Center, University of Texas

› Author Affiliations

Abstract

Full Text

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.

Figures

Fig. 1