According to results from the phase 3 HERTHENA-Lung02 trial, patritumab deruxtecan (HER3-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) when compared to platinum-based chemotherapy among patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had received prior EGFR tyrosine kinase inhibition.

These results will first be presented by Tony Mok, MD, PhD, Chinese University of Hong Kong, Hong Kong, China, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

According to Dr Mok et al, after progressing on a third-generation EGFR tyrosine kinase inhibitor, “available therapies provide limited efficacy” for patients with EGFR-mutant NSCLC. HER3-DXd is “an antibody-drug conjugate consisting of a fully human [monoclonal antibody] to HER3 attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker” that has showed promise in the previous HERTHENA-Lung01 trial.

The randomized, open-label phase 3 HERTHENA-Lumng03 study enrolled 586 patients with advanced EGFR-mutant NSCLC following disease progression on a third-generation EGFR tyrosine kinase inhibitor. Patients were randomized to receive either HER3-DXd or platinum-based chemotherapy. The primary end point was PFS as assessed by blinded independent central review. The key secondary end point was overall survival (OS).

With a median duration of follow-up of 10.7 months, the median treatment duration with HER3-DXd was 5.5 months and with platinum-based chemotherapy was 4.6 months. The median PFS with HER3-DXd was 5.8 months vs 5.4 months with platinum-based chemotherapy, representing a “significant improvement.” The PFS rate was 50% vs 38% at 6 months, 29% vs 19% at 9 months, and 18% vs 5% at 12 months, respectively. The objective response rate was 35.2% in the HER3-DXd arm and 25.3% in the platinum-based chemotherapy arm. The median duration of response was 5.7 months vs 5.4 months, respectively. The data for OS was immature at the time of the data-cut off.

The safety profile was manageable, and consistent with prior reports. Most common treatment-emergent adverse events were of hematologic and gastrointestinal nature.

Source:

Mok T, Yu H, Lim SM, et al. Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 8506.