Zongertinib in Previously Treated HER2-Mutant Non-Small-Cell Lung Cancer

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Innovative oral targeted therapies are needed for HER2-mutant non-small-cell lung cancer (NSCLC).
• Zongertinib is an oral, irreversible, HER2-selective tyrosine kinase inhibitor with demonstrated efficacy in advanced solid tumors with HER2 alterations.

Purpose of the Study:

• To evaluate zongertinib in a phase 1a-1b trial for patients with advanced or metastatic HER2-mutant NSCLC.
• To report the primary analysis of zongertinib in previously treated patients across different HER2 mutation types.

Main Methods:

• A multicohort, phase 1a-1b trial was conducted.
• Patients with HER2-mutant NSCLC received zongertinib at doses of 120 mg or 240 mg daily.
• Primary endpoint was objective response assessed by central or investigator review; secondary endpoints included duration of response and progression-free survival.

Main Results:

• In cohort 1 (75 patients), 71% achieved an objective response with a median response duration of 14.1 months and median progression-free survival of 12.4 months.
• Objective response rates were 48% in cohort 5 and 30% in cohort 3.
• Mainly low-grade drug-related adverse events were observed, with no cases of drug-related interstitial lung disease.

Conclusions:

• Zongertinib demonstrated clinical benefit in previously treated HER2-mutant NSCLC patients.
• The therapy showed promising response rates and progression-free survival.
• Adverse events were predominantly low-grade, indicating a favorable safety profile.