FDA

Hernexeos OK’d for HER2-mutant advanced NSCLC

August 14, 2025

Brand name: Hernexeos

Generic name: zongertinib

Manufacturer: Boehringer Ingelheim

Approval date: August 8, 2025

FDA granted accelerated approval to Hernexeos (zongertinib), a kinase inhibitor, 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-approved test, and who’ve received prior systemic therapy.

FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in detecting HER2 (ERBB2) TKD activating mutations in patients with non-squamous NSCLC who may be eligible for treatment with zongertinib.

Efficacy

Efficacy was evaluated in patients with unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD mutations who’d received prior systemic therapy and received zongertinib in Beamion LUNG-1 (NCT04886804), an open-label, multi-center, multi-cohort trial. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

Among 71 patients who received prior platinum-based chemotherapy but hadn’t been previously treated with a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate (ADC), ORR was 75% (95% CI, 63-83), with 58% having a DOR ≥6 months.

Among 34 patients previously treated with platinum-based chemotherapy and a HER2-targeted ADC, ORR was 44% (95% CI, 29-61), with 27% having a DOR ≥ 6 months.

Safety

The most common adverse reactions (≥20%) reported with zongertinib were diarrhea, hepatoxicity, rash, fatigue, and nausea. Grade 3 or 4 lab abnormalities included decreased lymphocytes, increased ALT and AST, decreased potassium, and increased GGT.

The prescribing information includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

Recommended dose

The recommended dosage of zongertinib is based on body weight. For patients weighing < 90 kg, the dose is 120 mg PO once daily. For patients weighing ≥ 90 kg, the dose is 180 mg PO once daily. Zongertinib may be taken with or without food and continued until disease progression or unacceptable toxicity.

Sources:

FDA grants accelerated approval to zongertinib for non-squamous cell NSCLC with HER2 TKD activating mutations. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations

Hernexeos (zongertinib) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219042s000lbl.pdf Revised August 2025. Accessed August 13, 2025.