FDA Grants Priority Review to Zongertinib in HER2-Mutant NSCLC

• The FDA accepted and granted priority review to the new drug application (NDA) for zongertinib (BI 1810631) for treating patients with unresectable or metastatic non–small cell lung cancer (NSCLC) harboring HER2 (ERBB2) mutations who have undergone prior systemic therapy.
• The phase Ib Beamion LUNG-1 trial (NCT04886804) serves as the basis for this regulatory decision as zongertinib showed a 71% response rate in this patient population.
• A Prescription Drug User Fee Act (PDUFA) decision is expected in the third quarter of 2025.

The FDA has accepted the NDA for zongertinib and granted it priority review for the treatment of adult patients with unresectable or metastatic NSCLC harboring HER2 (ERBB2) mutations who have undergone prior systemic therapy.¹

A PDUFA action date has been set for the third quarter of 2025.

“We believe zongertinib has the potential to transform the care of previously treated patients with HER2 (ERBB2)-mutant advanced non–small cell lung cancer and are hopeful about the continued research in other tumor types and lines of therapy,” said Shashank Deshpande, member of the board of managing directors and head of human pharma at Boehringer Ingelheim, in a press release. “Priority Review illustrates the urgent need in this patient population and the possibility for zongertinib to be a groundbreaking innovation for patients with limited treatment options.”

The NDA submission is supported by findings from the phase 1b Beamion LUNG-1 trial, specifically cohort 1 of the trial which consisted of 75 patients. Here, a promising objective response rate (ORR) of 71% was observed. Additionally, the 6-month progression-free survival (PFS) and duration of response (DoR) rates were 69% and 73%, respectively, in patients with HER2 tyrosine kinase domain mutations.

For safety, zongertinib had a favorable safety profile with minimal treatment-related discontinuations (3%) and dose reductions (5%). The most frequently observed treatment-related adverse events (TRAEs) included diarrhea (51%) and rash (27%), which were primarily low-grade. Only 1 patient experienced a grade 3 or higher TRAE, and no cases of treatment-related interstitial lung disease (ILD) were reported.

About the Beamion LUNG-1 Trial

Beamion LUNG-1 is a phase 1, open-label, dose-escalation trial evaluating zongertinib as monotherapy for the treatment of patients with advanced or metastatic solid tumors with HER2 aberrations.² This trial marks the first time zongertinib is being administered to humans.

Lung with cancer cells: © catalin - stock.adobe.com

The study consists of 2 phases. The first phase includes adults with various types of advanced solid tumors harboring HER2 gene alterations who have not responded to prior treatments. The second phase is enrolling patients with NSCLC carrying a specific HER2 mutation.

Patients aged 18 years and older are eligible for enrollment in the study if they have a histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-hematological malignancy, at least 1 measurable lesion according to RECIST v1.1, an ECOG score of 0, 1 or 2 (ECOG of 2 only for Cohorts 6 and 7), and adequate organ function. Patients must have recovered from any previous therapy-related toxicity to grade 1 or less at start of treatment and a life expectancy of at least 12 weeks at the start of treatment.

The primary end point of the first phase is to determine the maximum tolerated dose of zongertinib. Once established, this dose will be used in the second phase to assess the drug's efficacy in tumor reduction. The primary end point for the second phase is to evaluate objective response.

Patients are receiving zongertinib orally, either once or twice daily, and will continue treatment as long as they derive benefit and can tolerate it.

Ongoing Zongertinib Development

The FDA previously granted zongertinib breakthrough therapy and fast track designations. Japan’s Pharmaceuticals and Medical Devices Agency has also granted the agent an orphan drug designation.¹

Boehringer Ingelheim, the drug’s developer, continues to explore zongertinib’s efficacy in additional clinical settings, including the phase 3 Beamion LUNG-2 trial (NCT06151574), which is evaluating the agent’s efficacy compared with standard-of-care therapies for the treatment of patients with HER2 (ERBB2)-mutant NSCLC.

REFERENCES:

1. Boehringer’s zongertinib receives Priority Review from U.S. FDA for the treatment of HER2 (ERBB2)-mutant advanced non-small cell lung cancer. News release. February 19, 2025. Accessed February 19, 2025. https://tinyurl.com/7cbv9n3a

2. Beamion LUNG-1: A study to test different doses of zongertinib in people with different types of advanced cancer (solid tumours with changes in the HER2 gene). ClinicalTrials.gov. Updated February 10, 2025. Accessed February 19, 2025. https://clinicaltrials.gov/study/NCT04886804?tab=table