HER2 mutations account for approximately 2%–4% of non-small cell lung cancer (NSCLC) cases, and are more commonly seen in female, non-smoking, adenocarcinoma patients, often at a relatively younger age. These tumors tend to be aggressive with a high risk of brain metastases. Historically, first-line treatment for these patients mainly followed regimens for driver gene-negative NSCLC, with limited efficacy and a median progression-free survival of around 5–6 months.Now, a major breakthrough has arrived.

On May 21, 2026, China's National Medical Products Administration (NMPA) granted conditional approval for zongertinib (brand name: Hernexeos®) as a first-line treatment for advanced HER2-mutant non-small cell lung cancer. Guangzhou Royal Lee Cancer Hospital has completed the drug's pharmacy admission process and has already prescribed it to eligible patients, marking its official entry into clinical use.

First Oral HER2-Targeted Therapy: Precision Inhibition with Better Tolerability

Zongertinib is an oral, irreversible HER2-selective tyrosine kinase inhibitor (TKI) that precisely inhibits HER2 mutant signaling while sparing wild-type EGFR activity, thereby reducing common side effects such as rash and diarrhea associated with traditional targeted therapies. In simple terms, it acts like a "precision strike" against tumor cells carrying HER2 mutations, with less impact on normal cells.

The drug has received Breakthrough Therapy designations from both the U.S. FDA and China's NMPA. In 2025, it received accelerated approval from the FDA and conditional approval from the NMPA for previously treated patients. In February and May 2026, it received FDA and NMPA approvals respectively for first-line use, making it the world's first approved oral HER2 tyrosine kinase inhibitor.

Clinical Data: 76% Response Rate with Durable Efficacy 

The first-line approval was primarily based on results from the Beamion LUNG-1 study published in the New England Journal of Medicine (NEJM). Among 74 treatment-naïve patients with advanced HER2-mutant NSCLC:

- Objective response rate (ORR) reached 76%, with 11% complete responses and 65% partial responses

- Median duration of response was 15.2 months and median progression-free survival was 14.4 months, significantly longer than traditional chemotherapy (approximately 5–6 months)

- In patients with active brain metastases, the intracranial objective response rate reached 47% (assessed by RANO-BM criteria)

Safety: Adverse Events Mostly Mild to Moderate and Manageable 

Zongertinib has a generally manageable safety profile, with most adverse events being grade 1–2. The most common adverse event, diarrhea, was mostly mild to moderate (grade ≥3 in only 3%). No grade ≥3 rash was observed, and the discontinuation rate due to adverse events was low. With once-daily oral administration, it requires no hospitalization for infusion, making it convenient for home management.

Endorsed by Authoritative Guidelines 

- The NCCN Guidelines for Non-Small Cell Lung Cancer (Version 5.2026) list it as a first-line treatment recommendation for HER2-mutant advanced NSCLC and as a preferred option for previously treated patients

- The CSCO Guidelines for Non-Small Cell Lung Cancer (2026 Edition) list it as a Grade I recommendation for previously treated patients

Royal Lee in Action

Guangzhou Royal Lee Cancer Hospital, leveraging its JCI-accredited pharmaceutical management system, has completed the pharmacy admission of zongertinib (Hernexeos®) and has officially brought it into clinical use. As patient conditions vary significantly, whether this drug is appropriate for a given patient must be determined by a specialist physician based on comprehensive evaluation of genetic testing results and the individual's clinical condition.

Important Disclaimer: This article is intended for academic reference by healthcare professionals only and does not constitute individualized diagnostic or therapeutic advice, nor does it serve as any form of pharmaceutical advertisement or promotion. The efficacy and safety data presented are derived from clinical studies, and individual responses may vary. For specific information, please refer to the drug package insert approved by the National Medical Products Administration.