Evaluating Zongertinib After ADC Therapy: Efficacy, Safety, and ILD Considerations in HER2 Mutant NSCLC

In this segment, Dr. Jacob Sands reviews therapeutic decision-making for a patient with HER2 mutant non-small cell lung cancer progressing after trastuzumab deruxtecan. He highlights growing enthusiasm around zongertinib, a HER2-directed TKI that has demonstrated meaningful activity even in patients previously treated with antibody drug conjugates. He summarizes key clinical data, including median progression-free survival of 12.4 months, median duration of response of 14.1 months, and a 48 percent response rate in a small but informative cohort reported in the HAMAC publication. Dr. Sands emphasizes the drug’s generally manageable safety profile, with low-grade gastrointestinal and dermatologic toxicities and routine monitoring of liver function tests. He then contextualizes the patient’s prior grade 1 ILD, explaining how inflammatory findings can appear across treatments and why single-site, asymptomatic radiographic changes often do not preclude continued therapy. With confirmed progression and resolved ILD, he concludes that zongertinib represents a rational and well-tolerated next-line option.