FDA Grants Accelerated Approval to Zongertinib for HER2-Mutant NSCLC

The FDA has granted accelerated approval to zongertinib (Hernexeos; Boehringer Ingelheim Pharmaceuticals, Inc.) for adults with unresectable or metastatic non-squamous non–⁠small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.¹

The decision expands upon the drug’s August 2025 accelerated approval, which was granted for patients with HER2-mutant NSCLC who had received prior systemic therapy.² The previous approval was based on positive results from Beamion LUNG-1 (NCT04886804), a single-arm, open-label, multicenter, multicohort trial, with data presented at the 2024 World Conference on Lung Cancer and the 2025 American Association of Cancer Research (AACR) Annual Meeting.^3,2

“It’s very exciting for the first time to have an oral drug where the majority of patients are responding,” lead study author John V. Heymach, MD, PhD, said in an interview with The American Journal of Managed Care^® (AJMC^®) at the 2025 AACR Annual Meeting.⁴ “They’re having durable responses, and the toxicity for this drug is very limited; the safety profile is very manageable.”

Today’s approval was also based on data from Beamion LUNG-1.¹ Its application was a part of the FDA Commissioner’s National Priority Review Voucher pilot program, which is designed to accelerate the review of products that can potentially address key national priorities.

The Beamion LUNG-1 efficacy population included 72 patients with unresectable or metastatic nonsquamous NSCLC with HER2 (ERBB2) TKD mutations who had not yet received systemic therapy for advanced disease. The primary efficacy end points were objective response rate (ORR) and duration of response (DOR).

Among the study population, the ORR was 76% (95% CI, 65-85). In addition, 64% of patients had a DOR of at least 6 months, and 44% had a DOR of at least 12 months.

The recommended dosing for zongertinib is based on body weight. Specifically, patients weighing less than 90 kg should take 120 mg orally once daily, whereas those weighing 90 kg or more should take 80 mg orally once daily. The treatment may be taken with or without food and continued until disease progression or unacceptable toxicity. Warnings and precautions include hepatotoxicity, left ventricular dysfunction, embryo-fetal toxicity, and interstitial lung disease or pneumonitis.

“Zongertinib is setting a new standard as the first targeted therapy for treatment-naive patients with HER2-mutant advanced NSCLC with demonstrated efficacy, a manageable safety profile, and once-daily oral administration,” Heymach said in a news release.⁵ “Now these patients finally have a targeted treatment option that they can receive immediately following identification of a HER2 mutation.”

References

1. FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer. News release. FDA. February 26, 2026. Accessed February 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell
2. Caffrey M, McCormick B. Zongertinib granted accelerated approval in nonsquamous NSCLC for HER2 TKD-activating mutations. AJMC. August 8, 2025. Accessed February 26, 2026. https://www.ajmc.com/view/zongertinib-granted-accelerated-approval-in-nonsquamous-nsclc-for-her2-tkd-activating-mutations
3. Beamion LUNG-1: a study to test different doses of zongertinib in people with different types of advanced cancer (solid tumours with changes in the HER2 gene). ClinicalTrials.gov. Updated February 19, 2026. Accessed February 26, 2026. https://clinicaltrials.gov/study/NCT04886804
4. McCormick B, Heymach J. Zongertinib shows durable responses in previously treated HER2-mutated NSCLC: John Heymach, MD, PhD. AJMC. April 28, 2025. Accessed February 26, 2026. https://www.ajmc.com/view/zongertinib-shows-durable-responses-in-previously-treated-her2-mutated-nsclc-john-heymach-md-phd
5. FDA approves HERNEXEOS, the first targeted therapy for adults with HER2-mutant advanced NSCLC as an initial treatment option. News release. Boehringer Ingelheim. February 26, 2026. Accessed February 26, 2026. https://www.boehringer-ingelheim.com/us/human-health/cancer/lung-cancer/fda-approves-targeted-therapy-her2-mutant-advanced-nsclc