*August 2025*
Key Takeaways
- Zongertinib received FDA accelerated approval for HER2-mutant unresectable or metastatic nonsquamous NSCLC after prior systemic therapy.
- The phase 1 Beamion LUNG-1 trial showed a 71% objective response rate and favorable safety profile for zongertinib.
- Most treatment-related adverse effects were mild, with diarrhea and rash being the most common.
- Zongertinib is under investigation in a phase 3 trial comparing it to standard-of-care therapy for HER2-mutant NSCLC.
The FDA has granted accelerated approval to zongertinib (Hernexeos) for adult patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.1
The regulatory decision was based on findings from the phase 1 Beamion LUNG-1 trial (NCT04886804), an open-label, dose-escalation and dose-expansion study that evaluated zongertinib monotherapy in patients with advanced NSCLC harboring HER2 alterations.
Evaluable patients who received prior platinum-based chemotherapy and had not been previously treated with a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate (ADC; n = 71) achieved an overall response rate (ORR) of 75% (95% CI, 63%-83%). The 6-month duration of response (DOR) rate was 58%.
Those previously treated with platinum-based chemotherapy and a HER2-targeted ADC (n = 34) experienced an ORR of 44% (95% CI, 29%-61%), with a 6-month DOR rate of 27%.
Beamion LUNG-1 Overview
The Beamion LUNG-1 trial enrolled adults with histologically or cytologically confirmed unresectable or metastatic nonhematologic malignancies harboring HER2 mutations.3 Patients were required to have at least 1 measurable lesion per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.
In the dose-escalation phase, patients received increasing doses of zongertinib to determine the maximum tolerated dose (MTD). The expansion phase evaluated the optimal dose for efficacy and safety in HER2-mutant nonsquamous NSCLC following prior systemic therapy.
