FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations
Regulatory approval: On Aug 8, 2025, the FDA granted accelerated approval to zongertinib (Hernexeos) for adults with unresectable or metastatic non-squamous NSCLC harboring HER2 (ERBB2) TKD activating mutations (FDA-approved test) after prior systemic therapy. Approval was supported by Beamion LUNG-1 (NCT04886804), where ORR was 75% in patients previously treated with platinum chemotherapy (no prior HER2 TKI/ADC) and 44% in those previously treated with platinum plus a HER2-targeted ADC. The FDA also approved the Oncomine Dx Target Test as a companion diagnostic.
FDA accelerated approval: zongertinib for HER2 TKD–mutant non-squamous NSCLC
On Aug 8, 2025, 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-approved test, and who have received prior systemic therapy.
The FDA also approved the Oncomine Dx Target Test (Life Technologies) as a companion diagnostic to aid detection of HER2 (ERBB2) TKD activating mutations in non-squamous NSCLC patients who may be eligible for zongertinib.
Supporting evidence (Beamion LUNG-1)
Efficacy was evaluated in Beamion LUNG-1 (NCT04886804), an open-label, multi-center, multi-cohort trial in patients with unresectable/metastatic non-squamous NSCLC with HER2 TKD mutations who had received prior systemic therapy. Major endpoints were ORR and DOR by blinded independent central review per RECIST v1.1.
- Prior platinum; no prior HER2 TKI/ADC (n=71): ORR 75% (95% CI, 63–83); 58% had DOR ≥6 months.
- Prior platinum + HER2-targeted ADC (n=34): ORR 44% (95% CI, 29–61); 27% had DOR ≥6 months.
Label highlights
Warnings/precautions include hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity. The recommended dose is weight-based: 120 mg PO daily for <90 kg and 180 mg PO daily for ≥90 kg, taken with or without food, until progression or unacceptable toxicity.
The application received priority review and used RTOR; zongertinib previously received breakthrough therapy and fast track designations.