FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer

Regulatory approval: On Feb 26, 2026, the FDA granted accelerated approval to zongertinib (Hernexeos) for adults with unresectable or metastatic non-squamous NSCLC whose tumors harbor HER2 (ERBB2) tyrosine kinase domain activating mutations, detected by an FDA-authorized test. Approval was supported by the single-arm Beamion LUNG-1 trial (n=72), reporting ORR 76% (95% CI 65–85) with durability benchmarks at 6 and 12 months.

FDA accelerated approval (Feb 26, 2026)

The FDA granted accelerated approval to zongertinib (Hernexeos; Boehringer Ingelheim), a kinase inhibitor, for adults with unresectable or metastatic non-squamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.

The application was part of the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program and used expedited mechanisms including Real-Time Oncology Review (RTOR), Assessment Aid, priority review, and breakthrough therapy designation.

Evidence supporting approval

Efficacy was evaluated in Beamion LUNG-1 (NCT04886804), a single-arm, open-label, multicenter, multicohort trial. The efficacy population included 72 patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD mutations who had not received systemic therapy for advanced disease.

Primary outcome measures were ORR and DOR by blinded independent central review per RECIST v1.1:

  • ORR: 76% (95% CI, 65–85)
  • Among responders: 64% had DOR ≥6 months and 44% had DOR ≥12 months

Safety and dosing (label highlights)

Warnings/precautions include hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

Recommended dose is weight-based: 120 mg orally once daily if <90 kg; 180 mg once daily if ≥90 kg; may be taken with or without food, continued until progression or unacceptable toxicity. Full prescribing information will be posted on Drugs@FDA.

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