Zongertinib Wins Frontline NSCLC OK in Second CNPV Approval

The FDA has approved zongertinib (Hernexeos) for the treatment of patients with unresectable metastatic or non-squamous non–small cell lung cancer (NSCLC) with HER2 (ERBB2) tyrosine kinase domain (TKD)–activating mutations, per FDA-approved testing.¹ The approval marks the second under the FDA’s new Commissioner’s National Priority Voucher (CNPV) pilot program, following an application for the voucher filed on January 13, 2026.²

The efficacy of zongertinib was established in the single-arm, open-label, multicenter Beamion LUNG-1 trial (NCT04886804), which included 72 patients in its efficacy population.

The major efficacy outcomes evaluated were objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review per RECIST v1.1. An ORR of 76% (95% CI, 65%-85%) was observed, and 64% of patients whose disease responded to treatment had a DOR of at least 6 months; further, 44% of responders had a DOR of at least 12 months.

Patients included in the efficacy population (n = 72) had unresectable or metastatic, non-squamous NSCLC with HER2 (ERBB2) TKD mutations and had not received prior systemic therapy for advanced disease.

The recommended dose of zongertinib for patients weighing less than 90 kg is 120 mg orally once daily; for patients weighing at least 90 kg, the recommended dose is 180 mg once daily. The kinase inhibitor may be taken with or without food.

Serious adverse effects (AEs) include hepatotoxicity, left ventricular dysfunction, interstitial lung disease and pneumonitis, and embryo-fetal toxicity. Beyond serious risks, health care providers should be prepared to manage more common AEs observed in clinical data, including diarrhea, rash, fatigue, nausea, musculoskeletal pain, and upper respiratory tract infections.

This expanded indication follows a prior accelerated approval granted in August 2025 for patients who had already received systemic therapy. Treatment with the kinase inhibitor should generally continue until the patient experiences disease progression or unacceptable toxicity.

What Is the Commissioner’s National Priority Voucher program?

The CNPV pilot program was announced in June 2025, using a model similar to a tumor board review process to accelerate the review and approval of drugs addressing key needs in national health priorities, according to information from the FDA’s website.³

For a drug to be considered for CNPV, it must align with at least one of the following priorities: public health crisis response, innovative breakthrough therapy, large unmet medical needs, onshoring and supply chain resilience, or affordability.

Notably, drugs accepted for CNPV have a target 1- to 2-month turnaround time compared with 6 or more months in other priority review programs.

A final decision for this application was reached 44 days after filing through the CNPV pilot in conjunction with the Real-Time Oncology Review program, which streamlines data submission, and a voluntary Assessment Aid completed by the applicant, which facilitates the FDA’s review. Health care professionals are encouraged to report any suspected serious AEs to the FDA’s MedWatch Reporting System.

References

1. FDA grants accelerated approval to zongertinib for unresectable or metastatic non-squamous non-small cell lung cancer. FDA. February 26, 2026. Accessed February 26, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-unresectable-or-metastatic-non-squamous-non-small-cell
2. FDA grants second approval under the National Priority Voucher pilot program. News release. FDA. February 26, 2026. Accessed February 26, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-second-approval-under-national-priority-voucher-pilot-program
3. Commissioner's National Priority Voucher (CNPV) pilot program. FDA. Updated February 9, 2206. Accessed February 26, 2026. https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program