Zongertinib Earns Chinese Approval for Unresectable, Locally Advanced, HER2-Mutant NSCLC

China’s National Medical Products Administration (NMPA) has approved zongertinib tablets (Hernexeos) as a monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors have activating HER2 mutations and who have been treated with at least 1 previous line of systemic therapy.¹

Of note, this accelerated approval of zongertinib follows a breakthrough therapy designation and a priority review in China. The approval was supported by data from the phase 1b Beamion LUNG-1 trial (NCT04886804).

“The absence of a well-tolerated oral drug targeting HER2 has been a longstanding challenge in the treatment of NSCLC. The approval of zongertinib will change this landscape, setting a new treatment benchmark for HER2-mutant advanced NSCLC,” Yilong Wu, FACS, of Guangdong Provincial People’s Hospital and chairman of the Chinese Thoracic Oncology Group in China, stated in a news release. “This innovative drug provides a highly effective, targeted, oral treatment option for this patient population, which has an extremely poor prognosis and very limited treatment choices.”

Notably, on August 8, 2025, the FDA granted accelerated approval to zongertinib for the treatment of adult patients with unresectable or metastatic nonsquamous NSCLC whose tumors harbor HER2 tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have been treated with prior therapy.² This regulatory decision was also based on data from Beamion LUNG-1.

Data from the study revealed that among patients in cohort 1 treated with zongertinib at 120 mg daily (n = 75), the objective response rate (ORR) was 71% at the data cutoff date of November 29, 2024 (95% CI, 60%-80%).³ Specifically, 7% of patients achieved a complete response, and 96% of patients (95% CI, 89%-99%) achieved disease control. The median duration of response (DOR) was 14.1 months (95% CI, 6.9-not evaluable [NE]), and the median progression-free survival (PFS) was 12.4 months (95% CI, 8.2-NE). Furthermore, zongertinib had a low discontinuation rate of 3%.

Regarding safety, grade 3 or higher treatment-related adverse effects (TRAEs) were observed in 17% of patients in cohort 1.

Beamion LUNG-1 Study Design

The open-label study is evaluating the efficacy and safety of zongertinib for the treatment of patients 18 years of age or older with a histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic nonhematologic malignancy, with the presence of at least 1 measurable lesion per RECIST 1.1 criteria.⁴ Patients enrolled on the study are also required to be able to and willing to provide a sample of tumor for confirmation of HER2 status, and willing to comply with the protocol requirements for tumor biopsies. Other eligibility criteria include having an ECOG performance status of 0 to 2, adequate organ function, and having recovered from toxicities associated with previous therapy.

Notably, the phase 1b portion of the study includes 8 cohorts, with cohorts 6 and 8 only located in the United States, and cohort 7 only located in Japan. All patients receive zongertinib, regardless of cohort. In particular, patients in cohort 1 have tumors that harbor a HER2 mutation in the tyrosine kinase domain (TKD), cohort 5 includes patients with tumors that harbor a HER2 mutation in the TKD who were previously treated with a HER2-directed antibody-drug conjugate, and cohort 3 includes those with tumors harboring a non-TKD HER2 mutation.³ Moreover, patients in cohort 1 were initially randomly assigned to receive zongertinib at 120 mg or 240 mg once daily. In cohorts 5 and 3, patients initially received 240 mg of zongertinib once daily. Following the interim analysis data from cohort 1, all patients subsequently enrolled on the study received zongertinib at 120 mg daily.⁵

The primary end point was ORR by blinded independent central review in cohorts 1 and 5 or by investigator review in cohort 3. Secondary end points included DOR and PFS.

References

1. Boehringer’s Hernexeos approved in China as first oral targeted therapy for previously treated patients with HER2-mutant advanced NSCLC. News release. Boehringer Ingelheim. September 1, 2025. Accessed September 2, 2025. https://www.boehringer-ingelheim.com/human-health/cancer/lung-cancer/hernexeos-approved-china-targeted-therapy-nsclc
2. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed September 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations
3. Heymach JV, Ruiter G, Ahn M-J, et al. Zongertinib in patients with pretreated HER2-mutant advanced NSCLC: Beamion LUNG-1. Presented at: 2025 AACR Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract CT050.
4. Beamion LUNG-1: a study to test different doses of zongertinib in people with different types of advanced cancer (solid tumors with changes in the HER2 gene). ClinicalTrials.gov. Updated July 28, 2025. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT04886804
5. Heymach JV, Ruiter G, Ahn MJ, et al. Zongertinib in previously treated HER2-mutant non–small-cell lung cancer. N Eng J Med. 2025;392(23):2321-2333. doi:10.1056/NEJMoa2503704