FDA Approves Hernexeos for HER2-Mutant Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) has approved Hernexeos (zongertinib) for adults with unresectable or metastatic non-squamous non-small cell lung cancer whose tumors have specific HER2 (ERBB2) mutations, expanding access to the treatment for patients who have not previously received therapy.

The decision, announced by the FDA on Feb. 26, 2026, was made under the FDA’s new Commissioner’s National Priority Voucher pilot program to help speed the review of therapies that address critical health needs.

Hernexeos had previously received accelerated approval in August 2025 for adults with non-squamous non-small cell lung cancer and HER2 (ERBB2) tyrosine kinase domain activating mutations who had already received prior systemic therapy. The new accelerated approval extends the treatment option to previously untreated patients whose tumors test positive for these mutations using an FDA-authorized test.

The FDA granted the accelerated approval to Boehringer Ingelheim Pharmaceuticals, Inc.

Main data that support the findings

The approval was supported by clinical trial data submitted to the FDA showing that 76% of previously untreated patients experienced a substantial decrease in tumor size. According to the agency, this represents a significant improvement compared with the current standard of care, in which 30% to 45% of patients are typically expected to have this level of response.

Tumor shrinkage, often referred to as response rate, is one way researchers evaluate how well a treatment is working in clinical trials. In this case, more than three-quarters of patients who had not received prior therapy saw their tumors decrease substantially in size.

The FDA noted that lung cancer remains the leading cause of cancer-related death in the United States. According to the National Cancer Institute, there were an estimated 226,650 new diagnoses and 124,730 deaths from lung cancer in 2025. Hernexeos targets molecular alterations found in a subset of non-small cell lung cancers, offering a treatment option tailored to patients whose tumors carry HER2 (ERBB2) tyrosine kinase domain activating mutations.

Trial details

Hernexeos is approved for adults with unresectable or metastatic non-squamous non-small cell lung cancer whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-authorized test. Unresectable cancer refers to disease that cannot be removed with surgery, while metastatic cancer has spread to other parts of the body.

The application for this expanded use was filed Jan. 13, 2026. Under the Commissioner’s National Priority Voucher pilot program, the FDA issued a final decision 44 days after the filing date.

Hernexeos was proactively granted a national priority voucher Nov. 6, 2025, based on preliminary data. The Commissioner’s National Priority Voucher pilot program is designed to expedite review of applications that address national health priorities, including innovative therapies, large unmet medical needs, domestic manufacturing and affordability. Companies selected for the program receive a voucher that entitles them to benefits such as enhanced communication with the FDA and rolling review, which can shorten review timelines.

In addition to participating in the voucher program, Hernexeos received breakthrough therapy and priority review designations from the FDA, which are intended to facilitate development and speed review of certain drugs.

Safety

Serious side effects associated with Hernexeos include hepatotoxicity, left ventricular dysfunction, interstitial lung disease or pneumonitis and embryofetal toxicity.

The most common side effects reported with Hernexeos include diarrhea, rash, hepatotoxicity, fatigue, nausea, musculoskeletal pain and upper respiratory tract infection.

Patients with cancer and caregivers are encouraged to discuss potential benefits and risks with their health care team, including whether tumor testing for HER2 (ERBB2) mutations is appropriate and what side effects may occur with treatment.

References

1. “Hernexeos (zongertinib) Approval Under the Commissioner’s National Priority Voucher Pilot Program” FDA.

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