HERTHENA-Lung02: Phase III clinical trial of patritumab deruxtecan in advanced EGFR-mutated NSCLC following EGFR TKI therapy

This video article presents the phase III HERTHENA-Lung02 study protocol, investigating the use of patritumab deruxtecan (HER3-DXd) in EGFR-mutated non-small cell lung cancer (NSCLC).

First line treatment for NSCLC with the common EGFR gene activating mutations, exon 19 deletion and L858R substitution, is a third-generation EGFR tyrosine kinase inhibitor (TKI). Despite the high response rates seen in patients receiving a third-generation EGFR TKI, resistance typically occurs. Platinum-based chemotherapy is the standard-of-care treatment for patients that progress on a third-generation EGFR TKI, however antitumor efficacy is modest and transient. Additionally, resistance to third-generation EGFR TKIs is associated with a number of acquired genomic alterations. Therefore, this patient population is in need of novel treatments that are effective and durable and can address the diverse mechanisms of resistance to EGFR TKI therapy.

HER3-DXd is a HER3-directed antibody-drug conjugate that demonstrated clinically meaningful efficacy and a manageable safety profile in advanced EGFR-mutated NSCLC that progressed on EGFR TKI therapy and platinum-based chemotherapy. A recent clinical trial protocol manuscript, published in Future Oncology, detailed the rationale and design of the global, open-label, phase 3 HERTHENA-Lung02 trial evaluating the efficacy and safety of HER3-DXd compared with platinum-based chemotherapy in patients with EGFR-mutated NSCLC whose disease had progressed on or after treatment with EGFR TKI therapy, including a third-generation EGFR TKI.

Clinical Trial Registration: NCT05338970 (clinicaltrials.gov); 2021-005879-40 (EudraCT Number).

Contributors: Pasi A Jänne, Makoto Nishio, Silvia Novello, Martin Reck, Conor Steuer, Yi-Long Wu, Ronan Fougeray, Pang-Dian Fan, Jie Meng, David W Sternberg, Stephen Esker and Helena A Yu.

Original article(s):

Mok T, Jänne PA, Nishio M et al. HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI. Future Oncol. 2024;20(15):969-980. doi: 10.2217/fon-2023-0602.

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