FDA Approval Insights: Zongertinib for HER2 TKD–Mutated NSCLC: With Julia Rotow, MD; and Martin Dietrich, MD, PhD

Welcome to OncLive On Air®! I’m your host today, Caroline Seymour.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we spoke with Julia Rotow, MD, and Martin Dietrich, MD, PhD. Dr Rotow is the clinical director of the Lowe Center for Thoracic Oncology and director of clinical research at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. Dr Dietrich is a medical oncologist with The US Oncology Network Cancer Care Centers of Brevard and an assistant professor of internal medicine at the University of Central Florida College of Medicine in Orlando.

In our exclusive interview, Drs Rotow and Dietrich discussed the significance of the accelerated FDA approval of zongertinib (Hernexeos) for patients with HER2 TKD–mutated non–small cell lung cancer (NSCLC). They highlighted how this approval addresses a longstanding unmet need in a patient population that historically relied on chemotherapy-based approaches.

They noted that the introduction of zongertinib into the frontline setting represents a meaningful shift toward upfront biomarker-driven care, aligning HER2-positive disease with other oncogene-driven lung cancers where targeted therapies are used upfront.

The discussion also focused on efficacy findings from the pivotal phase 1b Beamion LUNG-1 trial (NCT04886804). In previously untreated patients with HER2 TKD mutations, zongertinib generated an objective response rate of 76% (95% CI, 65%-85%). The treatment also showed encouraging durability, with 64% of responders having a duration of response (DOR) lasting at least 6 months and 44% of responders having a DOR lasting at least 12 months.

Regarding safety, Rotow and Dietrich explained that zongertinib was designed as a HER2-selective inhibitor, potentially minimizing off-target EGFR-related toxicities. The most common adverse effects included low-grade diarrhea, rash, and liver enzyme elevations, with interstitial lung disease occurring infrequently. Notably, no significant signal for cardiac toxicity was observed, distinguishing zongertinib from some other HER2-directed therapies.

Finally, the experts underscored the importance of comprehensive biomarker testing to identify HER2 alterations and ensure that patients can benefit from these expanding targeted treatment options.

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