Skip to main content

Zongertinib Demonstrates Clinical Activity in HER2-Mutant Solid Tumors

*September 2023*

In patients with HER2–mutant non–small cell lung cancer (NSCLC) treated in a cohort of the phase 1a/b BEAMION Lung-1 trial (NCT04886804), treatment with zongertinib (BI 1810631) showed preliminary efficacy signals and acceptable, according to results of the the dose-escalation portion of the study.1

Treatment with zongertinib in the study will proceed to phase 1b evaluation at doses of 120 mg and 240 mg once daily in patients with HER2–mutant NSCLC.

Data from the trial, which were presented at the 2023 IASLC World Conference on Lung Cancer, demonstrated that at the data cutoff date of July 17, 2023, the maximum tolerated dose (MTD) had not been reached. On-treatment dose-limiting toxicities (DLTs) included grade 2 edema (n = 1; 60 mg twice daily); grade 2 diarrhea (n = 1; 150 mg twice daily); grade 3 platelet count decrease (n = 1; 360 mg once daily); and grade 3 alanine aminotransferase (ALT) increase, grade 2 blood bilirubin increase, and grade 2 aspartate aminotransferase (AST) increase (n = 1; 180 mg once daily).

“Zongertinib demonstrated encouraging preliminary antitumor activity in various tumors with HER2 aberrations in phase 1a, [and] very promising initial efficacy results were observed in phase 1b in pretreated patients with NSCLC harboring HER2 TKD mutations,” lead study author Noboru Yamamoto, MD, PhD, deputy director of the National Cancer Center Hospital and chief of the Department of Experimental Therapeutics in Tokyo, Japan, said in a presentation of the data.


Many solid tumors harbor HER2 mutations, approximately half of which are found in TKD. However, 90% of HER2 TKD mutations are exon 20 insertion mutations, which do not respond well to available TKIs and result in added gastrointestinal and skin toxicities as a result of wild-type EGFR inhibition. Read more.