On February 26, 2026, the FDA granted accelerated approval to zongertinib (Hernexeos), a kinase inhibitor, for adults with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD)-activating mutations. Tumor mutations must be identified using an FDA-authorized test. This approval expands the indication for zongertinib, which was evaluated under the FDA Commissioner’s National Priority Review Voucher pilot program, an initiative designed to expedite review of products addressing national health priorities.
The approval was based on findings from the Beamion LUNG-1 trial (NCT04886804), a single-arm, open-label, multicenter, multicohort study. The trial enrolled 72 treatment-naive patients with unresectable or metastatic nonsquamous NSCLC with HER2 TKD mutations. The major efficacy end points were objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review per RECIST v1.1.
Zongertinib demonstrated an ORR of 76% (95% CI, 65-85), with 64% of responders experiencing a DOR of at least 6 months, and 44% having a DOR of 12 months or longer.
The prescribing information includes warnings for potential adverse effects, including hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity. Patients receiving zongertinib should be monitored for these risks during treatment.
The recommended zongertinib dose is based on body weight:
- For patients <90 kg: 120 mg orally once daily
- For patients ≥90 kg: 180 mg orally once daily
The drug may be taken with or without food and continued until disease progression or the onset of unacceptable toxicity.
This accelerated approval provides a targeted treatment option for patients with HER2-mutated metastatic NSCLC, addressing an unmet need for a population with limited therapeutic options.
Source
- FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer. www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell