Zongertinib After ADC Therapy: Efficacy, Safety, and Clinical Context

This episode focuses on the clinical data supporting the use of zongertinib, a HER2-directed tyrosine kinase inhibitor (TKI), in HER2-mutant NSCLC. Dr Julia Rotow reviews multi-cohort trial results evaluating zongertinib across several patient subsets, including those with tyrosine kinase domain mutations, prior HER2-directed ADC exposure, CNS involvement, and treatment-naive metastatic disease. She highlights reported response rates, disease control outcomes, and progression-free survival, emphasizing how these data inform real-world sequencing decisions following ADC therapy. The discussion also contrasts zongertinib with earlier-generation HER2- or EGFR-targeted TKIs, noting how improved selectivity for HER2-mutant disease has contributed to a more favorable tolerability profile. Dr Rotow examines adverse events, such as gastrointestinal effects, rash, and liver function test elevations, and outlines monitoring considerations.