FDA Approves Hernexeos for Non-Squamous Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Hernexeos (zongertinib), which is a kinase inhibitor, for the treatment of adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations and who have received prior treatment.

Effectiveness of the drug was evaluated among patients with unresectable or metastatic non-squamous NSCLC with HER2 TKD mutations who had received prior systemic therapy and had received Hernexeos in the Beamion LUNG-1 clinical trial.

The objective response rate was 75% among 71 patients who had received previous platinum-based chemotherapy but not a HER2-targewted kinase inhibitor or antibody-drug conjugate, and the duration of response was at least six months for 58% of those patients.

The objective response rate was 44%, with 27% having a duration of response of at least six months, among the 34 patients who were previously treated with both platinum-based chemotherapy and a HER2-targeting antibody-drug conjugate.

The agency noted in its approval announcement that the recommended dosage is based on body weight, and prescribing information includes warnings and precautions for hepatotoxicity, left ventricular dysfunction, interstitial lung disease/pneumonitis and embryo-fetal toxicity.

Previous Efficacy Findings

Hernexeos has also shown clinically meaningful and durable responses in previously treated patients with HER2-mutated advanced NSCLC, according to findings presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting and published in The New England Journal of Medicine.

In the dose escalation portion of the phase 1 Beamion LUNG-1 trial, 75 patients were treated with Hernexeos. The objective response rate was 71%, which included a 7% complete response rate and a 64% partial response rate. Disease control was achieved in 96% of patients. Among 27 evaluable patients with brain metastases, 41% responded to treatment and 81% experienced disease control, highlighting potential intracranial activity.

Duration of response and progression-free survival were presented for the first time at AACR 2025, at 14.1 months and 12.4 months, respectively.

“These data presented at AACR 2025 suggest that Hernexeos may offer a new approach to treating patients with non-small cell lung cancer with activating HER2 mutations,” said the trial's coordinating investigator, Dr. John Heymach, said in news release from the biopharmaceutical company Boehringer Ingelheim. “Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, Hernexeos would be the first oral, targeted treatment option that addresses an unmet need for these patients.”

HER2, a protein that can be overexpressed in certain cancers, plays a key role in tumor growth and blood vessel formation. Hernexeos is designed to block HER2 signaling, which may result in tumor cell death.

The company noted that these results underscore Hernexeos’s potential role in advancing care for patients who have historically had limited targeted treatment options, according to the release.

Reference

1. “FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations,” FDA. Aug. 8, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.